Alzheimer’s disease (AD)-associated neurodegeneration is triggered by different fragments of amyloid beta (Aβ). Among them, Aβ (25–35) fragment plays a critical role in the development of neurodegeneration—it reduces synaptic integrity by disruption of excitatory/inhibitory ratio across networks and alters the growth factors synthesis. Thus, in this study, we aimed to identify the involvement of neurotrophic factors—the insulin-like growth factor 1 (IGF-1) and nerve growth factor (NGF)—of AD-like neurodegeneration induced by Aβ (25–35). Taking into account our previous findings on the neuroprotective effects of the mix of proteoglycans of embryonic genesis (PEG), it was suggested to test its regulatory effect on IGF-1 and NGF levels. To evaluate the progress of neurodegeneration, in vivo electrophysiological investigation of synaptic activity disruption of the entorhinal cortex–hippocampus circuit at AD was performed and the potential recovery effects of PEG with relative structural changes were provided. To reveal the direct effects of PEG on brain functional activity, the electrophysiological pattern of the single cells from nucleus supraopticus, sensomotor cortex and hippocampus after acute injection of PEG was examined. Our results demonstrated that after i.c.v. injection of Aβ (25–35), the level of NGF decreased in cerebral cortex and hypothalamus, and, in contrast, increased in hippocampus, prompting its multidirectional role in case of brain damage. The concentration of IGF-1 significantly increased in all investigated brain structures. The administration of PEG balanced the growth factor levels accompanied by substantial restoration of neural tissue architecture and synaptic activity. Acute injection of PEG activated the hypothalamic nucleus supraopticus and hippocampal neurons. IGF-1 and NGF levels were found to be elevated in animals receiving PEG in an absence of amyloid exposure. We suggest that IGF-1 and NGF play a critical role in the development of AD. At the same time, it becomes clear that the neuroprotective effects of PEG are likely mediated via the regulation of neurotrophins.

Autism spectrum disorders (ASD) are neurodevelopmental conditions involving impaired neuronal processes such as connectivity, synaptogenesis, and migration. Prenatal exposure to valproic acid (VPA), an anticonvulsant and mood stabilizer, is linked to increased ASD risk, with timing as a key factor. However, the molecular mechanisms of VPA-induced neurodevelopmental disruptions remain unclear. Building on our previous study, which characterized VPA-induced prenatal and postnatal ASD models with impaired social behavior, repetitive patterns, and altered brain connectivity, this study examines molecular changes in neurogenic brain regions. We analyzed the prefrontal cortex, hippocampus, and subventricular zone at key developmental time points (postnatal days 14 and 21), assessing neurotrophins (BDNF, Nt-3, IGF-β, GDNF) and markers of cell migration (DCX), differentiation (NeuN, GFAP), and synaptogenesis (synaptophysin). Our findings show that both prenatal and postnatal VPA exposure disrupt neurogenesis, with prenatal effects being more severe and persistent. Prenatal VPA significantly reduced BDNF in the subventricular zone and DCX in the olfactory bulb, suggesting impaired migration, while morphological analysis revealed thickening of ventricular lateral wall and disrupted cellular organization. Postnatal exposure led to transient neurotrophin changes, including delayed IGF-β production and an abnormal rise of BDNF levels. Elevated GFAP and reduced NeuN or synaptophysin in the prefrontal cortex, alongside increased neuronal markers in the hippocampus, suggest region-specific neuroglial imbalances. These findings highlight the stage-dependent vulnerability of the developing brain to VPA exposure, revealing distinct mechanisms of disruption in prenatal and postnatal administration. They underscore the need to minimize exposure risks during late gestation and early postnatal periods, which are crucial for neurodevelopment. Graphical Abstract Dynamic and comparative assessment of neurotrophins, neuroglial and synaptic markers, morphological changes both in prenatal and postnatal models of ASD. The graphical abstract illustrates the main significant changes observed in prenatal (left section) and postnatal (write section) models in comparison to the control (central section) group. In the middle (PND 14) and top rows (PND 21), the molecular and morphological changes schematically are illustrated in the relevant structures of the hemisphere (olfactory bulb, prefrontal cortex, subventricular zone, and hippocampus, respectively, from the left to the write). Morphological changes of neuronal cells are expressed by different colors: red neurons with abnormal morphology, and morphologically healthy transparent pink neurons. Slow migration of neuroblasts on the rostral way in prenatal (left section) and postnatal models (right section) is expressed by a red background in comparison with the green color in the control group (central section). The changes in protein levels are expressed by different numbers of cells. Decreased doublecortin level in the olfactory bulb on PND 21 is expressed by illustration of one cell instead of three as it is shown on PND 14. Changes in GFAP and NeuN, SYP markers indicating disbalance in the neuroglial ratio in the prefrontal cortex and hippocampus are expressed by comparatively different numbers of the cells (green astrocytes, red neurons). Inside the magnified synaptic clefts’ vesicles with the different numbers of SYP on the surface are illustrated. The level of neurotrophins in SVZ is expressed as three-color rectangular, which is compressed in prenatal (left middle section) and postnatal (right middle section) on PND 14 in comparison to the control group (central middle row).