Related Experiment Video
Updated: Aug 23, 2026
A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy
Published on: November 3, 2016
Neonatal handling increases sensitivity to acute neurodegeneration in adult rats
Katalin M Horvath1, Tibor Harkany, Jan Mulder
1Department of Molecular Neurobiology, Graduate School of Behavioral and Cognitive Neurosciences, University of Groningen, 9750 AA Haren, The Netherlands.
Insights
Neonatal handling in rats, previously shown to protect against aging, unexpectedly increased vulnerability to neurotoxic damage in adulthood. This suggests handling may prime the brain for heightened sensitivity to certain insults.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Perinatal environmental stimuli influence adult neural viability and cognitive function.
- Neonatal handling (NH) in rodents reduces stress reactivity and attenuates age-related neurodegeneration.
- The impact of NH on adult brain sensitivity to acute neurotoxic insults remains unclear.
Purpose of the Study:
- To investigate whether neonatal handling affects adult rats' susceptibility to an acute neurotoxic challenge.
- To determine if NH alters cholinergic system integrity following N-methyl-D-aspartate (NMDA) exposure.
Main Methods:
- Adult rats (11 months old), either neonatally handled or nonhandled controls, received unilateral NBM infusions of NMDA.
- Cholinergic cell and fiber loss were quantified in the nucleus basalis magnocellularis (NBM) and somatosensory cortex.
- Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) staining assessed neuronal integrity.
Main Results:
- No significant differences in cholinergic cell or fiber counts were observed in the nonlesioned hemisphere.
- Neonatally handled rats showed significantly greater loss of cholinergic fibers in the NBM and cortex of the lesioned hemisphere.
- This indicates enhanced vulnerability to NMDA-induced neurodegeneration in handled animals.
Conclusions:
- Neonatal handling enhances, rather than protects against, vulnerability to acute NMDA-induced neurotoxicity in adult rats.
- Findings contrast with NH's previously reported protective effects against spontaneous aging-related neurodegeneration.
- NH may prime the adult brain for increased susceptibility to specific neurotoxic insults.
Abstract:
Environmental stimuli during the perinatal period can result in persistent individual differences in neural viability and cognitive functions. Earlier studies have shown that brief daily maternal separation and/or handling of rat pups during the first weeks of life reduces stress reactivity during adulthood and attenuates neuronal loss and cognitive decline during aging. In the present study we examined whether neonatal handling also affects the sensitivity of the adult brain to an acute neurotoxic insult. Postnatally handled and nonhandled control rats were left undisturbed from weaning onwards until the age of 11 months. At this age, the animals were subjected to a neurotoxic challenge by unilateral infusion of 60 mM of the glutamate analogue N-methyl-D-aspartate (NMDA) into the nucleus basalis magnocellularis (NBM). The brains were collected to measure cholinergic cell and fiber loss. In the nonlesioned side of the brain, cholinergic cell number in the NBM and fiber density in the cortex were not different between postnatally handled and control rats. However, in the lesioned hemisphere handled animals exhibited a significantly higher loss of choline-acetyltransferase-immunoreactive and acetylcholinesterase-positive fibers in the somatosensory cortex. The present results provide evidence for an enhanced vulnerability of postnatally handled rats to acute neurodegeneration in contrast to the previously reported attenuation of spontaneous aging-related neurodegenerative processes.
