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Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adults, has a critical contribution to balanced excitatory-inhibitory networks in the brain. Alteration in depolarizing action of GABA during early life is connected to a wide variety of neurodevelopmental disorders. Additionally, the effects of postnatal GABA blockade on neuronal synaptic plasticity are not known and therefore, we set out to determine whether postnatal exposure to bicuculline, a competitive antagonist of GABA A receptors, affects electrophysiologic changes in hippocampal CA1 neurons later on. To this end, male and female Wistar rats received vehicle or bicuculline (300 μg/kg) on postnatal days (PNDs) 7, 9 and 11, and then underwent different behavioral and electrophysiological examinations in adulthood. Postnatal exposure to bicuculline did not affect basic synaptic transmission but led to a pronounced decrease in paired-pulse facilitation (PPF) in CA1 pyramidal neurons. Bicuculline treatment also attenuated the long-term potentiation (LTP) and long-term depression (LTD) of CA1 neurons accompanied by decreased theta-burst responses in male and female adult rats. These electrophysiology findings together with the reduced brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex reliably explain the disturbance in spatial reference and working memories of bicuculline-treated animals. This study suggests that postnatal GABA A blockade deteriorates short- and long-term synaptic plasticity of hippocampal CA1 neurons and related encoding of spatial memory in adulthood. • Postnatal blockade of GABA A receptor deteriorates the short-term synaptic plasticity and complex response profile of CA1 neurons in adulthood. • Neonatal GABA A blockade attenuates the LTP and LTD in SC–CA1 pathway. • Early life administration of bicuculline results in a deficit in spatial reference and working memories in adult rats. • Postnatal bicuculline decreases the BDNF levels in hippocampus and prefrontal cortex of adult rats. [ABSTRACT FROM AUTHOR]

Abstract: Alzheimer׳s disease (AD) is a neurodegenerative disorder with a progressive cognitive decline and memory loss. Multiple pathogenetic factors including aggregated β-amyloid (Aβ), neurofibrillary tangles (NFTs), cholinergic dysfunction and oxidative stress are involved in AD. Aβ, a major constituent of the senile plaques, is a potent neurotoxic peptide and has a pivotal role in cognitive deficit and reduced synaptic plasticity in AD. In the present study we examined the protective effect of troxerutin, as a multipotent bioflavonoid, on Aβ (1–42)-induced impairment of evoked field potential in hippocampal DG neurons. Male Wistar rats were divided into four groups including Aβ (42–1), Aβ (1–42), Aβ (1–42) plus troxerutin and Aβ (42–1) plus troxerutin groups. Aβ was injected intracerebroventricularly (i.c.v.) into right lateral ventricle and after two weeks the evoked field potential recorded from perforant path-DG synapses to assess paired pulse paradigm and long term potentiation (LTP). Administration of Aβ (1–42) drastically attenuated the LTP of DG neurons, while there was no significant difference in evoked field potentials between Aβ (1–42) plus troxerutin group with respect to Aβ (42–1) group. This study revealed that troxerutin improves the synaptic failure induced by Aβ peptide and can be introduced as a promising multi-potent pharmacological agent in prevention or treatment of AD in the future. [Copyright &y& Elsevier]