Eﬀect of food deprivation during early development on cognition
and neurogenesis in the rat
and Gregory L. Holmes
Department of Neurology, Columbia Presbyterian Hospital, New York, NY, USA
Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Hanover, NH, USA
Department of Neurology, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA
Received 25 January 2004; revised 22 March 2004; accepted 22 March 2004
Available online 6 May 2004
Food deprivation has been recognized as having pronounced beneﬁcial eﬀects in adult animals, increasing longevity, reducing
seizure susceptibility, and enhancing resistance to neurotoxins. It is not known whether food deprivation in developing animals is
neuroprotective or harmful. To evaluate the eﬀects of food deprivation on brain development, we evaluated visual–spatial learning
and memory and neurogenesis in the dentate gyrus of the hippocampus in food-deprived (FD) and well-fed (WF) rats. To induce
food deprivation, pups were removed from their dams for 12 hours per day from Postnatal Day (P) 2 to P19. FD and WF rat pups
were then subjected to status epilepticus (SE) induced by lithium–pilocarpine at P20. After SE, neurogenesis was measured, while in
another group of P38 rats, learning and memory were evaluated using the Morris water maze. Food deprivation was found to reduce
neurogenesis when assessed after the period of food deprivation. Although SE reduced neurogenesis in the WF animals, it had little
eﬀect additional to food deprivation on neurogenesis in the FD rats. Compared with the WF group, FD rats had a mild impairment
in memory in the water maze testing after SE. Our study demonstrates that food deprivation during the neonatal period in rats is
associated with a decrease in neurogenesis and mild impairment of visual–spatial memory. Although SE decreased neurogenesis in
the WF group, in FD animals, SE did not reduce neurogenesis more than what was seen with food deprivation alone. Our results
suggest that although food deprivation during early development reduces dentate gyrus neurogenesis, the reduced neurogenesis is
not a major factor in cognitive impairment after SE in FD rats.
Ó 2004 Elsevier Inc. All rights reserved.
Keywords: Neurogenesis; Status epilepticus; Memory; Learning; Food deprivation; Caloric restriction; Malnourishment; Nutrition
Caloric or food deprivation consists of underfeeding
and has been recognized as having pronounced beneﬁ-
cial eﬀects in animals . Food deprivation signiﬁcantly
increases the survival of laboratory animals by delaying
the aging process [2–4], improving immunological status
, reducing tumor growth [4,6], and enhancing genomic
stability . In rats, brain damage can be reduced and
behavioral outcome improved by food deprivation prior
to exposure to the mitochondrial toxins 3-nitropropr-
ionic acid and malonate . Recently, Greene et al. 
demonstrated that caloric restriction in juvenile EL
mice, a genetic model of multifactorial idiopathic epi-
lepsy, has a pronounced antiepileptogenic eﬀect, delay-
ing the onset of epilepsy.
There have been few studies examining food restric-
tion in developing animals. It is known that nutritional
insults early in life have a profound and often perma-
nent eﬀect on the subsequent development of the brain
[10,11]. In clinical studies, malnourished children have
more learning and behavioral problems than well-
nourished children [12,13]. Studies have shown that
malnutrition during the period of brain growth results in
disturbances of anatomical, biochemical, and behavioral
development . However, it is important to note that
caloric restriction diﬀers from severe fasting or starva-
tion in that caloric restriction reduces food intake
Corresponding author. Fax: 1-603-659-6233.
E-mail addresses: Gregory.L.Holmes@Dartmouth.Edu, gregory.l.
firstname.lastname@example.org (G.L. Holmes).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
Epilepsy & Behavior 5 (2004) 446–454