Altered balance of γ‐aminobutyric acidergic and glutamatergic afferent inputs in rostral ventrolateral medulla‐projecting neurons in the paraventricular nucleus of the hypothalamus of renovascular hypertensive rats

Abstract

An imbalance of excitatory and inhibitory functions has been shown to contribute to numerous pathological disorders. Accumulating evidence supports the idea that a change in hypothalamic γ-aminobutyric acid (GABA)-ergic inhibitory and glutamatergic excitatory synaptic functions contributes to exacerbated neurohumoral drive in prevalent cardiovascular disorders, including hypertension. However, the precise underlying mechanisms and neuronal substrates are still not fully elucidated. In the present study, we combined quantitative immunohistochemistry with neuronal tract tracing to determine whether plastic remodeling of afferent GABAergic and glutamatergic inputs into identified RVLM-projecting neurons of the hypothalamic paraventricular nucleus (PVN-RVLM) contributes to an imbalanced excitatory/inhibitory function in reno-vascular hypertensive rats (RVH). Our results indicate that both GABAergic and glutamatergic innervation densities increased in oxytocin-positive, PVN-RVLM (OT-PVN-RVLM) neurons in RVH rats. Despite this concomitant increase, time-dependent and compartment-specific differences in the reorganization of these inputs resulted in an altered balance of excitatory/inhibitory inputs in somatic and dendritic compartments. A net predominance of excitatory over inhibitory inputs was found in OT-PVN-RVLM proximal dendrites. Our results indicate that, along with previously described changes in neurotransmitter release probability and postsynaptic receptor function, remodeling of GABAergic and glutamatergic afferent inputs contributes as an underlying mechanism to the altered excitatory/ inhibitory balance in the PVN of hypertensive rats.

Circulating Angiotensin II Gains Access to the Hypothalamus and Brain Stem During Hypertension via Breakdown of the Blood–Brain Barrier

“…Immunofluorescence (Table.S1) was performed for cell-type identification, and examined by confocal microscopy (LSM510, Zeiss Microimaging) 25 . BBB permeability was assessed based on the detection of fluorescent-dye staining within brain microvasculature or parenchyma 26 .…”

“…The extravasated FITC10 signal was isolated using a digital subtraction procedure, and the proportion of FITC10-stained pixels in the subtracted image was calculated and compared among experimental groups. A densitometry analysis was used to compare differences in BBB protein constituents or immunoreactivity between WKYs and SHRs and results were expressed as % area within the nucleus occupied by the detected immunoreactivity 25 .…”

Cross talk between AT1receptors and Toll-like receptor 4 in microglia contributes to angiotensin II-derived ROS production in the hypothalamic paraventricular nucleus

“…Immunofluorescence was examined with an upright Zeiss LSM510 confocal microscope as previously described (4). Images from consecutive optical focal planes were taken (for hypothalamic 200-m sections: 40 images, 2-m intervals; for 30-m sections: 20 images, 1 m-intervals; for isolated microglial cells: 6 images, 1-m intervals), and a projection image of the sections was then generated.…”

Metabolic syndrome as a risk factor for neurological disorders

“…However, in animal models two important components of MetS (hyperinsulinemia and hypertension) have been related to activation of glutamatergic receptors in the rostral ventrolateral medulla, increasing the sympathoexcitatory response activity [184]. Furthermore, an altered balance of gamma-aminobutyric acidergic (GABA) and glutamatergic afferent inputs in the rostral ventrolateral medulla, projecting neurons in the paraventricular nucleus of the hypothalamus, has also been observed [185]. However, further investigations are needed to clarify this relationship and for better understanding of whether metabolic changes could be predictive of an increased risk to develop mood disorders and vice-versa.…”