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Updated: Sep 10, 2026
Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
Early neonatal 192 IgG saporin induces learning impairments and disrupts cortical morphogenesis in rats
Laura Ricceri1, Christine Hohmann, Joanne Berger-Sweeney
1Section of Comparative Psychology, Laboratory Fisiopatologia OS, Istituto Superiore di Sanità, Vle Regina Elena 299, I-00161 Rome, Italy. laura.ricceri@iss.it
Insights
Early neonatal exposure to 192 IgG saporin in rats impairs cognitive development and alters brain structure, with effects more pronounced than later exposures. This provides a model for neurodevelopmental disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurotoxicology
Background:
- Neonatal intraventricular injections of 192 IgG saporin on postnatal day 7 (pnd 7) cause cholinergic loss and learning deficits.
- The effects of earlier immunotoxin administration during critical neocortical maturation stages were investigated.
Purpose of the Study:
- To analyze the behavioral, morphological, and neurochemical effects of early neonatal intraventricular injection of 192 IgG saporin (pnd 1 and 3).
- To determine if earlier lesions result in more profound behavioral impairment compared to later lesions.
Main Methods:
- Passive avoidance (PA) learning, locomotor activity, and novelty reactivity were assessed in rats.
- Choline acetyltransferase (ChAT) activity was measured in basal forebrain targets.
- Morphological analysis of the somatosensory cortex was performed.
Main Results:
- Early 192 IgG saporin administration led to slower PA task acquisition in females, with no effect on retention or locomotion.
- Mild impairment in spatial novelty reaction was observed in lesioned rats by pnd 180.
- Marked ChAT reduction in hippocampus and neocortex, and sex-specific cortical thickness alterations were noted.
Conclusions:
- Interrupting cholinergic innervation during early postnatal development impacts cognitive behavior, neurochemistry, and cortical organization in a sex-specific manner.
- Early-life cholinergic system disruption causes more profound cortical alterations than later lesions.
- These findings offer a potential model for neurodevelopmental disorders associated with mental retardation.
Abstract:
We have shown previously that neonatal intraventricular injections of the selective cholinergic immunotoxin 192 IgG saporin on postnatal day 7 (pnd 7) induce marked cholinergic loss in hippocampus and neocortex and a learning impairment on pnd 15. In the present study, we analysed the behavioural, morphological and neurochemical effects of earlier intraventricular injection of the immunotoxin 192 IgG saporin (pnd 1 and 3). We hypothesised that these earlier lesions would interrupt a critical stage in neocortical maturation, and impair behavior more profoundly than the later lesions. Passive avoidance (PA) learning and locomotor activity during the PA test were assessed on pnd 15. Retention of the PA task was assessed on pnd 16. Reactivity to spatial and object novelty was assessed on pnd 180 in a spatial open field test with five objects. Choline acetyltransferase (ChAT) activity was measured in basal forebrain targets on pnd 20 and pnd 180. Neonatal administration of 192 IgG saporin resulted in a slower acquisition of the PA task in females; retention and locomotor activity were not affected. On pnd 180, reaction to spatial novelty was mildly impaired in lesioned rats of both sexes. There was a marked reduction of ChAT in the hippocampus and neocortex of lesioned rats of both sexes, at both ages. Morphological analysis of the somatosensory cortex of lesioned rats revealed alterations in cortical development with sex specific variations in total cortical thickness. These results suggest that interrupting cholinergic basal forebrain innervation of neocortex and hippocampus during the first postnatal days affects the development of cognitive behaviour, neurochemistry and cortical organisation in a sex specific manner. Furthermore, the alterations in cortical organization are more profound than those noted after a lesion later in postnatal development. These behavioural and morphological abnormalities could be considered a model for several neurodevelopmental disorders associated with mental retardation.
