Male mice placed on a ketogenic diet from postnatal day (P) 21 through adulthood have reduced growth, are hypoactive, show increased freezing in a conditioned fear paradigm, and have spatial learning deficits.

Abstract:

:The ketogenic diet (KD) is a non-pharmacological treatment for specific types of epilepsy. In addition, it has been shown to be effective in mitigating other neurologic disorders. The KD is also effective in reducing body mass, leading to an increase in use by the general population for weight loss. As the popularity of the clinical and general use of the KD has increased, it is important to develop adequate mouse models to better understand the effects of the KD in both normal and diseased states. Many times, the best outcome for disorders treatable with the KD would be achieved by commencing treatment in early life. Few studies have evaluated the cognitive effect of starting the KD in early life. To better understand these effects, male C57BL6/J mice were placed on a KD from postnatal day (P) 21 through young adulthood (~P90). KD-fed mice had increased blood ketone levels, reduced blood glucose, and reduced weight gain versus mice fed a control diet (CD). The weight loss in the KD-fed mice was not accompanied by a change in body fat percentage, suggesting that there was a loss of lean mass. Behavioral testing began on P60 while the mice were still on the diet. KD-fed mice were hypoactive with CD-fed mice. In the Morris water maze, KD-fed mice showed decreased path efficiency, suggesting a spatial learning deficits. No differences were observed in spatial memory or in novel object recognition memory. In a contextual and conditioned fear paradigm, the KD-fed mice had an increase in freezing behavior. These data suggest that early-life exposure to a KD leads to impaired body composition and long-term cognitive changes.

journal_name

Brain Res

journal_title

Brain research

authors

Miles KN,Skelton MR

doi

10.1016/j.brainres.2020.146697

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

146697

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(20)30053-6

journal_volume

1734

pub_type

杂志文章
  • Escapable and inescapable stress differentially alter extracellular levels of 5-HT in the basolateral amygdala of the rat.

    abstract::The effects of escapable and yoked inescapable electric tailshocks on extracellular levels of serotonin (5-HT) in the basolateral amygdala were measured by in vivo microdialysis. Inescapable, but not escapable, shock increased extracellular 5-HT in the amygdala relative to restrained controls. Basal levels of 5-HT wer...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(98)00960-3

    authors: Amat J,Matus-Amat P,Watkins LR,Maier SF

    更新日期:1998-11-23 00:00:00

  • Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

    abstract::Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mam...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(98)00613-1

    authors: Massari VJ,Dickerson LW,Gray AL,Lauenstein JM,Blinder KJ,Newsome JT,Rodak DJ,Fleming TJ,Gatti PJ,Gillis RA

    更新日期:1998-08-17 00:00:00

  • Muscle spindle number is normal in guinea pigs with reduced dorsal root ganglia following in utero deprivation of nerve growth factor.

    abstract::Muscle spindles are induced during embryonic development by contact between sensory axons and undifferentiated myotubes. Neonatal guinea pigs deprived of nerve growth factor in utero can have only 15-20% of the normal number of dorsal root ganglion cells. This study demonstrates that such neonates have normal numbers ...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(88)90945-6

    authors: Laing NG,Osborne PA,Johnson EM Jr

    更新日期:1988-03-22 00:00:00

  • Stimulus-response functions in areas with experimentally induced referred muscle pain--a psychophysical study.

    abstract::Few clinical or experimental studies have carried out systematic investigations of cutaneous and deep sensibility in areas with referred muscle pain. Therefore, no clear signs of increased or decreased psychophysical responses to various somatosensory stimuli are found in referred pain areas. In the present study, a t...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(96)01077-3

    authors: Graven-Nielsen T,Arendt-Nielsen L,Svensson P,Jensen TS

    更新日期:1997-01-02 00:00:00

  • Group III mGluR-mediated depression of sensory synaptic transmission.

    abstract::The effect of L-AP4, a group III mGluR agonist, on sensory synaptic transmission in the lamprey spinal cord has been analyzed. Paired recordings were made between cutaneous mechanosensory neurons (dorsal cells) and postsynaptic spinobulbar giant interneurons. L-AP4 reduced the monosynaptic dorsal cell-evoked EPSP, but...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(02)02462-9

    authors: Krieger P,El Manira A

    更新日期:2002-05-24 00:00:00

  • Anterograde tracing of retinohypothalamic afferents with Fluoro-Gold.

    abstract::The anterograde neuronal tracing properties of Fluoro-Gold (FG) were characterized in this study by its ability to label the retinohypothalamic tract (RHT) upon pressure injection of the substance into the vitrous body of the eye in the Djungarian hamster, Phodopus sungorus. Tracing was compared to the anterograde neu...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(96)01151-1

    authors: Reuss S,Decker K

    更新日期:1997-01-16 00:00:00

  • Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats.

    abstract::The present experiments were designed to assess whether brain hypothermia can reduce the behavioral and histopathological deficits associated with global forebrain ischemia. Animals were subjected to 12.5 min of four vessel occlusion (4VO) with moderate hypotension, and brain temperature maintained at either 37 degree...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(92)90945-6

    authors: Green EJ,Dietrich WD,van Dijk F,Busto R,Markgraf CG,McCabe PM,Ginsberg MD,Schneiderman N

    更新日期:1992-05-15 00:00:00

  • Neurally mediated hyperactive voiding in spontaneously hypertensive rats.

    abstract::The development of hypertension in spontaneously hypertensive rats (SHR) and hyperactive voiding in rats with urethral obstruction are characterized by abnormal smooth muscle growth, increased tissue levels of nerve growth factor (NGF) and altered patterns of innervation. The present study was undertaken to determine ...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(98)00061-4

    authors: Spitsbergen JM,Clemow DB,McCarty R,Steers WD,Tuttle JB

    更新日期:1998-04-20 00:00:00

  • Partial antagonism of 8-OH-DPAT'S effects on male rat sexual behavior with a D2, but not a 5-HT1A, antagonist.

    abstract::The serotonin agonist 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), injected systemically or directly into the medial preoptic area (MPOA), reduces the ejaculatory threshold in male rats. While 8-OH-DPAT has been characterized as an agonist at the 5-HT1A receptor, it also acts at other receptor sites including the dop...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(98)01331-6

    authors: Matuszewich L,Lorrain DS,Trujillo R,Dominguez J,Putnam SK,Hull EM

    更新日期:1999-02-27 00:00:00

  • Studies on dopamine turnover in ovariectomized or hypophysectomized female rats. Effects of 17 beta-estradiol benzoate, ethynodioldiacetate and ovine prolactin.

    abstract::The effects of 17 beta-estradiol benzoate (EB), ethynodioldiacetate and ovine prolactin on dopamine (DA) turnover have been studied. As an index for a change in turnover, differences in DA depletion following tyrosine hydroxylase inhibition with alpha-methyl-tyrosine methylester were observed. DA was measured by means...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(78)90728-x

    authors: Wiesel FA,Fuxe K,Hökfelt T,Agnati LF

    更新日期:1978-06-16 00:00:00

  • Neurochemical properties of the prolactin releasing peptide (PrRP) receptor expressing neurons: evidence for a role of PrRP as a regulator of stress and nociception.

    abstract::In addition to its stimulatory effect on prolactin release, the neuropeptide prolactin releasing peptide (PrRP) has been shown to be a mediator of the stress response. To analyze the neurochemical properties of the cells responsive to PrRP and involved in stress modulation, we examined PrRP receptor co-expression with...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(02)03183-9

    authors: Lin SH,Leslie FM,Civelli O

    更新日期:2002-10-11 00:00:00

  • Involvement of medial septal glutamate and GABAA receptors in behaviour-induced acetylcholine release in the hippocampus: a dual probe microdialysis study.

    abstract::In the present study, the role of medial septal receptors in behaviour-induced increase in acetylcholine (ACh) release in hippocampus was investigated using dual-probe microdialysis in combination with a simple behavioural procedure. gamma-Aminobutyric acid (GABA) and glutamate receptor agonists and antagonists were a...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(97)01445-5

    authors: Moor E,Schirm E,Jacsó J,Westerink BH

    更新日期:1998-04-06 00:00:00

  • Axonal projections of X-cells to the superior colliculus and to the nucleus of the optic tract in cats.

    abstract::Axonal projections of ganglion cells to the superior colliculus (SC) and to the nucleus of the optic tract (NOT) were re-examined physiologically in the cat's retina. Taking care to minimize current spreads around the stimulating electrodes placed in the NOT or the SC, we reached a conclusion that a substantial propor...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(85)91465-9

    authors: Sawai H,Fukuda Y,Wakakuwa K

    更新日期:1985-08-19 00:00:00

  • Regional distribution of copper, zinc and iron in the brain in Long-Evans Cinnamon (LEC) rats with a new mutation causing hereditary hepatitis.

    abstract::In Long-Evans Cinnamon (LEC) rats of three different ages (7, 13 and 32 weeks old) concentrations of Cu, Zn and Fe were measured in 8 regions of the brain. The LEC groups aged 7 and 13 weeks showed low concentrations of Cu in all regions compared to Long-Evans Agouti (LEA) rats. In 32-week-old LEC rats, however, Cu co...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(92)91587-5

    authors: Sugawara N,Ikeda T,Sugawara C,Kohgo Y,Kato J,Takeichi N

    更新日期:1992-08-21 00:00:00

  • Sex differences in the dendritic branching of dentate granule cells following differential experience.

    abstract::Male and female hooded rats were raised from weaning in either a complex or an isolated environment in two separate replications. After one month, the brains were Golgi-Cox stained and dendritic fields of dentate gyrus granule cells were quantified. There was a sex difference in response to the environment. Females ra...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(85)90125-8

    authors: Juraska JM,Fitch JM,Henderson C,Rivers N

    更新日期:1985-04-29 00:00:00

  • Evidence that 4S RNA is axonally transported in normal and regenerating rat sciatic nerves.

    abstract::Studies in regenerating goldfish optic nerves indicate that RNA may be axonally transported during optic nerve regeneration14,18,19. The present study was performed to determine if the axonal migration of RNA could be demonstrated during regeneration of the rat sciatic nerve. Rats, which had only the left sciatic nerv...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(79)90652-8

    authors: Lindquist TD,Inogoglia NA

    更新日期:1979-04-20 00:00:00

  • Differential effects of inorganic lead on hippocampal long-term potentiation in young rats in vivo.

    abstract::Tetanic stimulation at 50 Hz elicited long-term potentiation (LTP) in the hippocampal CA1 region of 28-day-old control animals. In contrast, no significant potentiation was seen following the same tetanus in animals chronically exposed to 1000 ppm of lead acetate during development. Gender differences were observed in...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(00)02657-3

    authors: Zaiser AE,Miletic V

    更新日期:2000-09-08 00:00:00

  • Attenuation by PACAP of glutamate-induced neurotoxicity in cultured retinal neurons.

    abstract::The effects of pituitary adenylate cyclase activating polypeptides (PACAPs: PACAP27, PACAP38) on glutamate-induced neurotoxicity were examined using cultured retinal neurons obtained from 3- to 5-day old Wistar rats. Cell viability was evaluated by double staining with fluorescein diacetate and propidium iodide. Effec...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(99)01690-x

    authors: Shoge K,Mishima HK,Saitoh T,Ishihara K,Tamura Y,Shiomi H,Sasa M

    更新日期:1999-08-21 00:00:00

  • Rat optic nerve: freeze-fracture studies during development of myelinated axons.

    abstract::This freeze-fracture study examines the development of myelinated fibers in the rat optic nerve. Axolemma of optic nerve fibers were studied before, during, and after myelination. At birth, the optic nerve is composed entirely of non-myelinated (premyelinated) axons, while in the adult, virtually all fibers acquire co...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(82)90948-9

    authors: Black JA,Foster RE,Waxman SG

    更新日期:1982-10-28 00:00:00

  • Expression of c-fos in the rat brainstem after chronic intermittent hypoxia.

    abstract::Chronic intermittent hypoxia (CIH) may cause sustained systemic hypertension by increasing sympathetic neural discharge (SND). We hypothesized that CIH alters brainstem circuits modulating SND. After 30 days of CIH exposure in rats, increased c-fos labeling was seen in the nucleus of the solitary tract and ventrolater...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(98)01222-0

    authors: Greenberg HE,Sica AL,Scharf SM,Ruggiero DA

    更新日期:1999-01-23 00:00:00

  • Complementary mosaic distributions of thalamic and nigral axons in the caudate nucleus of the cat: double anterograde labeling combining autoradiography and wheat germ-HRP histochemistry.

    abstract::The discontinuous terminal distributions of thalamo- and nigrostriatal axons were examined in adjacent tissue sections from single cat brains by combined anterograde labeling with tritiated proline autoradiography and wheat germ-horseradish peroxidase histochemistry. Injection of one tracer into the centromedian-paraf...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(85)90287-2

    authors: Beckstead RM

    更新日期:1985-05-27 00:00:00

  • Identification of opioid peptides regulating proliferation of neurons and glia in the developing nervous system.

    abstract::Endogenous opioid systems (i.e. opioids and opioid receptors) play a role in regulating neural development. Using the cerebellar cortex of 6-day-old rats, the most potent opioid peptides involved with cell proliferation were assessed. In both the external germinal (granule) layer (EGL), a germinative matrix giving ris...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(91)91585-o

    authors: Zagon IS,McLaughlin PJ

    更新日期:1991-03-01 00:00:00

  • The relationship between white matter brain metabolites and cognition in normal aging: the GENIE study.

    abstract::Magnetic resonance spectroscopy (MRS) has demonstrated age-related changes in brain metabolites that may underlie micro-structural brain changes, but few studies have examined their relationship with cognitive decline. We performed a cross-sectional study of brain metabolism and cognitive function in 82 healthy adults...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/j.brainres.2007.06.027

    authors: Charlton RA,McIntyre DJ,Howe FA,Morris RG,Markus HS

    更新日期:2007-08-20 00:00:00

  • Effect of chronic sympathetic denervation on cerebrovascular hypertrophy during the development of hypertension in rats.

    abstract::The present study was designed to examine the trophic effect of sympathetic nerves on cerebrovascular hypertrophy in developmental hypertension. Unilateral superior cervical ganglionectomy was performed in spontaneously hypertensive rats at 4 weeks of age, and wall-to-lumen ratios of cerebral arteries were determined ...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(86)90772-9

    authors: Sadoshima S,Fujii K,Yao H,Ibayashi S,Fujishima M

    更新日期:1986-08-06 00:00:00

  • Cytokines regulate c-Met expression in cultured astrocytes.

    abstract::We investigated c-Met expression in cultured astrocytes and their regulation by cytokines. Immunocytochemistry revealed that c-Met was expressed in cultured astrocytes. Western blotting revealed that acidic and basic fibroblast growth factor (FGF) enhanced and hepatocyte growth factor (HGF) reduced c-Met expression. R...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/s0006-8993(02)03975-6

    authors: Shimazaki K,Yoshida K,Hirose Y,Ishimori H,Katayama M,Kawase T

    更新日期:2003-02-07 00:00:00

  • Signalling pathways in the nitric oxide donor-induced dopamine release in the striatum of freely moving rats: evidence that exogenous nitric oxide promotes Ca2+ entry through store-operated channels.

    abstract::We showed previously, using in vitro microdialysis, that the activation of the soluble guanylate cyclase (sGC)/cyclic GMP pathway was the underlying mechanism of the extracellular Ca(2+)-dependent effects of exogenous NO on dopamine (DA) secretion from PC12 cells. In this study, the co-infusion of the sGC inhibitor 1H...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/j.brainres.2004.07.040

    authors: Rocchitta G,Migheli R,Mura MP,Esposito G,Desole MS,Miele E,Miele M,Serra PA

    更新日期:2004-10-15 00:00:00

  • Microwave irradiated collagen tubes as a better matrix for peripheral nerve regeneration.

    abstract::Collagen is one of the best materials used for nerve guide preparation due to its biocompatibility and desirable tensile strength. In this work, we have compared regeneration and functional reinnervation after sciatic nerve resection with bioresorbable crosslinked collagen guides in 10 mm gap. The crosslinking was car...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/j.brainres.2005.03.022

    authors: Ahmed MR,Vairamuthu S,Shafiuzama M,Basha SH,Jayakumar R

    更新日期:2005-06-07 00:00:00

  • Opioid receptor regulation of 5-hydroxytryptamine release from the rat hippocampus measured by in vivo microdialysis.

    abstract::The modulation of serotonin (5-HT) release by opioid receptors in the hippocampus of the awake, unrestrained rat was evaluated by use of in vivo microdialysis. The hippocampus was perfused with Ringer's solution (2 microliters/min), and extracellular levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid ...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0006-8993(93)90456-w

    authors: Yoshioka M,Matsumoto M,Togashi H,Smith CB,Saito H

    更新日期:1993-06-04 00:00:00

  • Mitotic cycling of radial glial cells of the fetal murine cerebral wall: a combined autoradiographic and immunohistochemical study.

    abstract::Radial glial cells of the embryonic murine cerebral wall are selectively labeled by staining with antibody RC1. In order to study the mitotic cycling of these cells, we combined RC1 immunohistochemistry and autoradiographic analysis following [3H]thymidine injection at 1, 2, 6, 48 h prior to sacrifice. Many radial gli...

    journal_title:Brain research

    pub_type: 杂志文章

    doi:10.1016/0165-3806(88)90043-0

    authors: Misson JP,Edwards MA,Yamamoto M,Caviness VS Jr

    更新日期:1988-02-01 00:00:00

  • Rodent models of TDP-43: recent advances.

    abstract::Recently, missense mutations in the gene TARDBP encoding TDP-43 have been linked to familial ALS. The discovery of genes encoding these RNA binding proteins, such as TDP-43 and FUS/TLS, raised the notion that altered RNA metabolism is a major factor underlying the pathogenesis of ALS. To begin to unravel how mutations...

    journal_title:Brain research

    pub_type: 杂志文章,评审

    doi:10.1016/j.brainres.2012.04.031

    authors: Tsao W,Jeong YH,Lin S,Ling J,Price DL,Chiang PM,Wong PC

    更新日期:2012-06-26 00:00:00