Transient sublethal hypoxia in neonatal rats causes reduced dendritic spines, aberrant synaptic plasticity, and impairments in memory

Abstract

Hypoxic/ischemic insult, a leading cause of functional brain defects, has been extensively studied in both clinical and experimental animal research, including its etiology, neuropathogenesis, and pharmacological interventions. Transient sublethal hypoxia (TSH) is a common clinical occurrence in the perinatal period. However, its effect on early developing brains remains poorly understood. The present study was designed to investigate the effect of TSH on the dendrite and dendritic spine formation, neuronal and synaptic activity, and cognitive behavior of early postnatal Day 1 rat pups. While TSH showed no obvious effect on gross brain morphology, neuron cell density, or glial activation in the hippocampus, we found transient hypoxia did cause significant changes in neuronal structure and function. In brains exposed to TSH, hippocampal neurons developed shorter and thinner dendrites, with decreased dendritic spine density, and reduced strength in excitatory synaptic transmission. Moreover, TSH‐treated rats showed impaired cognitive performance in spatial learning and memory. Our findings demonstrate that TSH in newborn rats can cause significant impairments in synaptic formation and function, and long‐lasting brain functional deficits. Therefore, this study provides a useful animal model for the study of TSH on early developing brains and to explore potential pharmaceutical interventions for patients subjected to TSH insult.

Cirbp-PSD95 axis protects against hypobaric hypoxia-induced aberrant morphology of hippocampal dendritic spines and cognitive deficits

“…Studies on primary hippocampal neurons showed that hypoxia caused dentritic spines density decreasing. These observations of hypoxia-inhibited development of dendritic spines were consistent with previous studies [ 30 , 31 ], which demonstrate that disturbance of spine morphology after hypobaric hypoxia might be associated with impairment of cognitive functions.…”

Comparative Milestones in Rodent and Human Postnatal Central Nervous System Development

“…For example, while severe neonatal hypoxia causes obvious lesions of hemorrhage and necrosis, 39 mild hypoxia results in delayed dendritic development and reduced neuronal activity, without obvious effects on neuronal number, microglia, or gross alterations in brain growth. 40…”