Evolution of Brain Morphology in Spontaneously Hypertensive and Wistar-Kyoto Rats From Early Adulthood to Aging: A Longitudinal Magnetic Resonance Imaging Study

The influence of hypertension and aging alone on brain structure has been described extensively. Our understanding of the interaction of hypertension with aging to brain morphology is still limited. We aimed to detect the synergistic effects of hypertension and aging on brain morphology and to describe the evolution patterns of cerebral atrophy from spatial and temporal perspectives. In 8 spontaneously hypertensive rats (SHRs) and 5 Wistar-Kyoto rats, high-resolution magnetic resonance imaging scans were longitudinally acquired at 10, 24, 52, and 80 weeks. We analyzed the tissue volumes of gray matter, white matter, cerebral spinal fluid, and total intracranial volume (TIV), and then evaluated gray matter volume in detail using voxel-based morphometry (VBM) and region of interest-based methods. There were interactive effects on hypertension and aging in tissue volumes of gray matter, white matter, and TIV, of which gray matter atrophy was most pronounced, especially in elderly SHRs. We identified the vulnerable gray matter volume with combined effects of hypertension and aging in the septal region, bilateral caudate putamen, hippocampus, primary somatosensory cortex, cerebellum, periaqueductal gray, right accumbens nucleus, and thalamus. We automatically extracted the septal region, anterior cingulate cortex, primary somatosensory cortex, caudate putamen, hippocampus, and accumbens nucleus and revealed an inverted-U trajectory of volume change in SHRs, with volume increase at the early phase and decline at the late phase. Hypertension interacts with aging to affect brain volume changes such as severe atrophy in elderly SHRs.

Whole-Brain Afferent Inputs to the Caudate Nucleus, Putamen, and Accumbens Nucleus in the Tree Shrew Striatum

Day-active tree shrews have a well-developed internal capsule (ic) that clearly separates the caudate nucleus (Cd) and putamen (Pu). The striatum consists of the Cd, ic, Pu, and accumbens nucleus (Acb). Here, we characterized the cytoarchitecture of the striatum and the whole-brain inputs to the Cd, Pu, and Acb in tree shrews by using immunohistochemistry and the retrograde tracer Fluoro-Gold (FG). Our data show the distribution patterns of parvalbumin (PV), nitric oxide synthase (NOS), calretinin (CR), and tyrosine hydroxylase (TH) immunoreactivity in the striatum of tree shrews, which were different from those observed in rats. The Cd and Pu mainly received inputs from the thalamus, motor cortex, somatosensory cortex, subthalamic nucleus, substantia nigra, and other cortical and subcortical regions, whereas the Acb primarily received inputs from the anterior olfactory nucleus, claustrum, infralimbic cortex, thalamus, raphe nucleus, parabrachial nucleus, ventral tegmental area, and so on. The Cd, Pu, and Acb received inputs from different neuronal populations in the ipsilateral (60, 67, and 63 brain regions, respectively) and contralateral (23, 20, and 36 brain regions, respectively) brain hemispheres. Overall, we demonstrate that there are species differences between tree shrews and rats in the density of PV, NOS, CR, and TH immunoreactivity in the striatum. Additionally, we mapped for the first time the distribution of whole-brain input neurons projecting to the striatum of tree shrews with FG injected into the Cd, Pu, and Acb. The similarities and differences in their brain-wide input patterns may provide new insights into the diverse functions of the striatal subregions.

Spatial relationship between the c-Fos distribution and enkephalinergic, substance P, and tyrosine hydroxylase innervation fields after acute treatment with neuroleptics olanzapine, amisulpride, quetiapine, and aripiprazole in the rat septum

Objective. The aim of the present study was to demonstrate the spatial relationship between the c-Fos immunoreactive cells elicited by an acute treatment with neuroleptics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI) and enkephalinergic (ENK), substance P (SP), and tyrosine hydroxylase (TH) innervation fields in the rat septum.Methods. Male Sprague Dawley rats received a single injection of OLA (5 mg), ARI (10 mg), AMI (20 mg), QUE (15 mg/kg/b.w.). Ninety min after antipsychotics administration, the animals were transcardially perfused with a fixative and the brains cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black endproduct. Afterwards, the sections were exposed to ENK, SP, and TH antibodies and the reaction product visualized by biotin-labeled fluorescent AlexaFluor 564 dye. The data were evaluated from the sections either simultaneously illuminated with fluorescent and transmission microscope beams or after merging the separately illuminated sections in the Adobe Photoshop 7.0 software.Results. ENK, SP, and TH displayed characteristic spatial images formed by a dense accumulation of immunoreactive fibers and terminals on the both sides of the septum. A dense plexus of axons formed by ENK and SP immunopositive terminals were situated predominantly in the lateral, while TH ones more medial portion of the septum. QUE and AMI activated distinct amount of c-Fos expression in cells located within the SP-immunoreactive principal innervation field. The OLA effect on the c-Fos expression was very pronounced in the ventral TH-labeled principal innervation field including the space between the ENK field ventral portion and the dorsal margin of the accumbens nucleus shell. Generally, the occurrence of c-Fos cells in the ENK-immunoreactive principal innervation field, in comparison with the surrounding septal area, was less abundant after all of the four antipsychotics treatments.Conclusion. The data of the present study indicate that ENK, SP, and TH innervation fields may influence separate populations of septal cells activated by AMI, OLA, QUE, and ARI and that each of these region-differently innervated cells may be associated with the functional heterogeneity of the individual lateral septal nuclei.