Effect of senescence on the tyrosine hydroxylase and S100B immunoreactivity in the nigrostriatal pathway of the rat.

Senescence is a natural and progressive physiological event that leads to a series of morphophysiological alterations in the organism. The brain is the most vulnerable organ to both structural and functional changes during this process. Dopamine is a key neurotransmitter for the proper functioning of the brain, directly involved in circuitries related with emotions, learning, motivation and reward. One of the main dopamine- producing nuclei is the substantia nigra pars compacta (SNpc), which establish connections with the striatum forming the so-called nigrostriatal pathway. S100B is a calcium binding protein mainly expressed by astrocytes, involved in both intracellular and extracellular processes, and whose expression is increased following injury in the nervous tissue, being a useful marker in altered status of central nervous system. The present study aimed to analyze the impact of senescence on the cells immunoreactive for tyrosine hydroxylase (TH) and S100B along the nigrostriatal pathway of the rat. Our results show an decreased expression of S100B+ cells in SNpc. In addition, there was a significant decrease in TH immunoreactivity in both projection fibers and TH+ cell bodies. In the striatum, a decrease in TH immunoreactivity was also observed, as well as an enlargement of the white matter bundles. Our findings point out that senescence is related to the anatomical and neurochemical changes observed throughout the nigrostriatal pathway.

S100B protein: general characteristics and pathophysiological implications in the Central Nervous System.

BACKGROUND: Calcium-binding proteins are heterogeneous proteins that act binding this ion in specific domains, performing numerous functions. OBJECTIVE: In the present review, we aim to gather principal information about S100B protein in the Central Nervous System (CNS), highlighting its particularities, mapping, functionalities, and consequences on CNS dysfunction. METHODS: The research was carried out by searching Pubmed, Medline, Science Direct, Lilacs, the Cochrane Library, and Web of Science databases using the following descriptors: S100 protein; Central Nervous System; Nervous Lesions, as well as their corresponding terms in Portuguese and Spanish. The terms were first searched separately, then together. RESULTS: Due to its ability to bind with calcium, S100B is involved in the regulation of several intra- and extracellular physiological processes. As well as being multifunctional, this protein can be considered both a "marker" and "signaling" since it is capable of triggering functions of detection of and protection in situations of injury to the CNS. CONCLUSIONS: In-depth studies are necessary to discover the innumerable actions of this protein which are still unknown. It is expected that these can bring varied benefits by elucidating its therapeutic potential in preclinical and clinical situations.

Aging Alters Daily and Regional Calretinin Neuronal Expression in the Rat Non-image Forming Visual Thalamus.

Aging affects the overall physiology, including the image-forming and non-image forming visual systems. Among the components of the latter, the thalamic retinorecipient inter-geniculate leaflet (IGL) and ventral lateral geniculate (vLGN) nucleus conveys light information to subcortical regions, adjusting visuomotor, and circadian functions. It is noteworthy that several visual related cells, such as neuronal subpopulations in the IGL and vLGN are neurochemically characterized by the presence of calcium binding proteins. Calretinin (CR), a representative of such proteins, denotes region-specificity in a temporal manner by variable day-night expression. In parallel, age-related brain dysfunction and neurodegeneration are associated with abnormal intracellular concentrations of calcium. Here, we investigated whether daily changes in the number of CR neurons are a feature of the aged IGL and vLGN in rats. To this end, we perfused rats, ranging from 3 to 24 months of age, within distinct phases of the day, namely zeitgeber times (ZTs). Then, we evaluated CR immunolabeling through design-based stereological cell estimation. We observed distinct daily rhythms of CR expression in the IGL and in both the retinorecipient (vLGNe) and non-retinorecipient (vLGNi) portions of the vLGN. In the ZT 6, the middle of the light phase, the CR cells are reduced with aging in the IGL and vLGNe. In the ZT 12, the transition between light to dark, an age-related CR loss was found in all nuclei. While CR expression predominates in specific spatial domains of vLGN, age-related changes appear not to be restricted at particular portions. No alterations were found in the dark/light transition or in the middle of the dark phase, ZTs 0, and 18, respectively. These results are relevant in the understanding of how aging shifts the phenotype of visual related cells at topographically organized channels of visuomotor and circadian processing.

Pattern of tyrosine hydroxylase expression during aging of mesolimbic pathway of the rat.

Senescence is a physiological and progressive event that leads to the impairment of normal functions of the organism. The nervous system is one of the most affected systems during aging, presenting both structural and functional alterations associated with a decline in normal brain functions. In the present study we aimed to evaluate the impact of senescence on the mesolimbic pathway (nucleus accumbens - NAc and ventral tegmental area - VTA) of the rat, through immunohistochemistry for tyrosine hydroxylase (TH) enzyme, in young (3 months old), middle-aged (10 months old) and aged animals (18 months old). There was a significant decrease in the TH-immunoreactivity across NAc in aged animals as compared to the young and middle-aged ones, as revealed by optical densitometry. Medium and caudal regions of the VTA in the young animals possessed a higher number of TH-immunoreactive neurons as compared to the more aged groups. Comparisons among VTA regions in young animals revealed a difference in the number of cell bodies when the medium region was compared to the rostral and caudal regions whilst in both the middle-aged and aged groups comparisons between rostral vs caudal and medium vs caudal regions were significant. Our results show that aging impacts the mesolimbic pathway across its rostrocaudal axis, with a decrease of TH-reactivity in NAc and loss of neurons in VTA. These events may be involved with behavioral alterations observed throughout aging.

Region-specific glial hyperplasia and neuronal stability of rat lateral geniculate nucleus during aging.

The normal aging process is accompanied by functional declines in image-forming and non-image forming visual systems. Among the components of these systems, the thalamic lateral geniculate nucleus (LGN) offers a good model for aging studies since its three anatomical subdivisions, namely dorsal lateral geniculate nucleus (dLGN), intergeniculate leaflet (IGL) and ventral lateral geniculate nucleus (vLGN), receives light information from retina and projects to different brain areas involved in visual-related functions. Nevertheless, there is very little data available about quantitative morphological aspects in LGN across lifespan. In this study, we used design-based stereology to estimate the number of neurons, glial cells, the glia/neuron ratio and the volume of the LGN of Wistar rats from 3, 13 or 23months of age. We examined each LGN subdivision processed by immunohistochemistry for NeuN and Nissl counterstain. We observed no significant age-related neuronal loss in any nuclei and a 21% and 33% significant increase in dLGN and IGL glial cells of 23month-old rats. We also observed the glia/neuron relation increases in dLGN of 13month-old rats and in dLGN, IGL and vLGN internal portion of 23month-old ones. Moreover, we report an age-related increase in IGL volume. These results show region-specific glial hyperplasia during aging within LGN nuclei, perhaps due to compensatory responses to inflammation. In addition, we observed the glia/neuron ratio as a more sensitive parameter to quantify age-related alterations. Hence, we provide an updated and expanded quantitative characterization of these visual-related thalamic nuclei and its variability across lifespan.

Morphological changes in the suprachiasmatic nucleus of aging female marmosets (Callithrix jacchus).

The suprachiasmatic nuclei (SCN) are pointed to as the mammals central circadian pacemaker. Aged animals show internal time disruption possibly caused by morphological and neurochemical changes in SCN components. Some studies reported changes of neuronal cells and neuroglia in the SCN of rats and nonhuman primates during aging. The effects of senescence on morphological aspects in SCN are important for understanding some alterations in biological rhythms expression. Therefore, our aim was to perform a comparative study of the morphological aspects of SCN in adult and aged female marmoset. Morphometric analysis of SCN was performed using Nissl staining, NeuN-IR, GFAP-IR, and CB-IR. A significant decrease in the SCN cells staining with Nissl, NeuN, and CB were observed in aged female marmosets compared to adults, while a significant increase in glial cells was found in aged marmosets, thus suggesting compensatory process due to neuronal loss evoked by aging.

Retinal projections and neurochemical characterization of the pregeniculate nucleus of the common marmoset (Callithrix jacchus).

In mammals, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian timing system. The SCN is the site of the endogenous biological clock that generates rhythms and synchronizes them to environmental cues. The IGL is a key structure that modulates SCN activity and is responsible for the transmission of non-photic information to the SCN, thus participating in the integration between photic and non-photic stimuli. Both the SCN and IGL receive projections of retinal ganglion cells and the IGL is connected to the SCN through the geniculohypothalamic tract. Little is known about these structures in the primate brain and the pregeniculate nucleus (PGN) has been suggested to be the primate equivalent of the rodent IGL. The aim of this study was to characterize the PGN of a primate, the common marmoset (Callithrix jacchus), and to analyze its retinal afferents. Here, the marmoset PGN was found to be organized into three subsectors based on neuronal size, pattern of retinal projections, and the distribution of neuropeptide Y-, GAD-, serotonin-, enkephalin- and substance P-labeled terminals. This pattern indicates that the marmoset PGN is equivalent to the IGL. This detailed description contributes to the understanding of the circadian timing system in this primate species considering the importance of the IGL within the context of circadian regulation.