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Tlenek azotu, komorki kosci i ich umieranie

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Early life stress disrupts development of the human and animal brain and increases the risk of psychophysiological disorders and susceptibility to addiction in adulthood. Maternal separation (MS), an animal model of early life stress, was shown to raise predisposition to addictive behaviours and change neuronal activity as well as dendritic spine density in a range of brain structures. Mesocorticolimbic dopaminergic pathways originating from the ventral tegmental area (VTA) play a crucial role in the development of addiction, however, the influence of MS on VTA neuronal architecture remains obscure. AIM(S): The current study aimed to verify the influence of MS on VTA neuronal dendritic spine density, a possible anatomical substrate of functional changes in the ascending dopaminergic pathways. METHOD(S): Female rat pups were separated from dams for 3 hours daily from PND2 to 14. At PND65, rats were decapitated, Golgi-Cox staining was performed, and the density of spines was calculated manually on I‑III‑ order dendrites. Given the functional and anatomical heterogeneity of the VTA, analyzed neurons were assigned to specified VTA sub‑regions. RESULTS: In rats subjected to MS, significantly lower density of dendritic spines on neurons in ventromedial (II‑order branches – 15%), dorsolateral (II‑ and III‑order segments – 24 – 23% respectively), and dorsomedial (I‑order branches – 25%) VTA, was observed when compared to control. No significant changes in spine density were observed in ventrolateral VTA (only 6% decrease in spine density). CONCLUSIONS: The observed decrease in dendritic spine density in VTA neurons can be linked to a reduced number of excitatory synapses that may underlie altered activity of mesocorticolimbic pathways, altered dopamine release, and increased susceptibility to addictions observed after MS and childhood trauma. Sub‑region specificity of observed changes points to varied sensitivity of VTA neurons to stress. FINANCIAL SUPPORT: Funding: NSC-Poland UMO‑2016/21/B/NZ4/00204.
BACKGROUND AND AIMS: Repeated and chronic forms of stress constitute a major risk factor in serious pathologies including depression, cognitive impairments and motor control dysfunctions. However, the mechanisms of the influence of prolonged elevation of the level of corticosteroid hormones on synaptic transmission in the cerebral cortex remain poorly understood. METHODS: We studied the effects of the treatment of male Wistar rats with corticosterone for 7 days on excitatory and inhibitory synaptic inputs as well as on the excitability of layer II/ III pyramidal neurons of the rat motor cortex. Spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) were recorded from pyramidal cells in ex vivo slices of the rat frontal cortex, prepared 2 days after the last administration of the hormone. RESULTS: Corticosterone treatment induced an increase in the frequency but not the amplitude of sEPSCs. Measurements with the use of tetrodotoxin (TTX) revealed that most of the recorded sEPSCs represented miniature EPSCs (mEPSCs). The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells remained unchanged. Corticosterone treatment modified neither the density of dendritic spines on pyramidal neurons nor the protein density levels of selected subunits of AMPA, NMDA and GABAA receptors. CONCLUSIONS: Thus, prolonged administration of exogenous corticosterone selectively enhances glutamatergic transmission in the rat motor cortex, most likely via an enhancement of spontaneous glutamate release from presynaptic terminals. Support: National Science Centre, Poland, grant UMO-2012/07/B/ NZ4/01669
INTRODUCTION: Stress-related elevated glucocorticoid level disrupts performance of motor tests in rats but underlying neuronal mechanisms remain unknown. Repeated corticosterone injections serve as an animal model of prolonged stress. Recently we have shown that treatment with corticosterone influences both the electrophysiology and morphology of pyramidal neurons of rat primary motor cortex (M1). It enhances spontaneous glutamate release and has no effect on dendritic spine density in superficial layers of M1, whereas in deep layers it increases spine density but does not affect electrophysiology AIM(S): The current study aimed at identification of spine types in different layers of M1 and consequent judgment on their ability to form functional synapses. Investigating the density of various spine types would clarify the apparent discrepancy between our previous electrophysiological and morphological data. METHOD(S): Rats were injected with corticosterone for 7 days, twice-daily (control group received the vehicle) and then decapitated. Brains were removed and stained using the Golgi-Cox method. Images of layer II/III and V M1 pyramidal neurons were obtained and deconvolved. Mushroom, stubby and thin spines and filopodia were counted manually on representative dendrites from the apical and basal part of the neurons. RESULTS: In layer II/III of M1 the density of each morphological spine type remained unaltered by corticosterone treatment, however, it significantly elevated the density of thin spines in layer V neurons. Other spine types were not affected. CONCLUSIONS: These data suggest that previously observed increase in M1 layer V spine density was caused exclusively by thin spine number upsurge. Thin spines are considered immature and do not form functional synaptic connections, what further validates our previous electrophysiological data. Lack of morphological changes in layer II/III is congruent with the proposed corticosterone-induced pre-synaptic mechanism of enhanced glutamate release.
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