Hypothalamic Lateral Tuberal Nucleus Research Articles

Neurons and Glial Cells of the Lateral Tuberal Hypothalamic Nucleus in Vascular Dementia

The aim was to study the size and density of neurons and glial cells of the hypothalamic lateral tuberal nucleus (LTN) in vascular dementia (VD), which is the second most common dementia. Material and methods. The density of neurons and glial cells, the cross-sectional area of nuclei, nucleoli and perikarya of LTN neurons were determined in patients with VD (n=10) and in the control group of individuals (n=10) who did not have any neurological or cognitive dysfunction. Comparison of indicators between groups was carried out using ANOVA and Student's t-test. Results. In VD cases all of the studied morphometric parameters of neurons and their density were decreased by within 20% (p<0.02). An increase in the neuroglial index by an average of 27% (p=0.04) was also noted. Сhanges in the size of neurons and nucleoli were observed regardless of the gender of patients. However, a decrease in the neuronal density (p = 0,008) and an increase in the neuroglial index (p=0,03) were noted only in the group of female patients. Conclusion. VD leads to a decrease in the metabolic activity of neurons of the hypothalamus and of the lateral tuberal nucleus, in particular. Moreover, a part of LTN neurons dies inducing a compensatory and adaptive increase in the population of glial cells. Thus, some late manifestations of VD, such as asthenia and increased exhaustion, may be caused, at least in part by a decrease in the neuronal activity and reorganization of intercellular interactions in the LTN.

Mapping key neuropeptides involved in the melanocortin system in Atlantic salmon (Salmo salar) brain.

The melanocortin system is a key regulator of appetite and food intake in vertebrates. This system includes the neuropeptides neuropeptide y (NPY), agouti-related peptide (AGRP), cocaine- and amphetamine-regulated transcript (CART), and pro-opiomelanocortin (POMC). An important center for appetite control in mammals is the hypothalamic arcuate nucleus, with neurons that coexpress either the orexigenic NPY/AGRP or the anorexigenic CART/POMC neuropeptides. In ray-finned fishes, such a center is less characterized. The Atlantic salmon (Salmo salar) has multiple genes of these neuropeptides due to whole-genome duplication events. To better understand the potential involvement of the melanocortin system in appetite and food intake control, we have mapped the mRNA expression of npy, agrp, cart, and pomc in the brain of Atlantic salmon parr using in situ hybridization. After identifying hypothalamic mRNA expression, we investigated the possible intracellular coexpression of npy/agrp and cart/pomc in the tuberal hypothalamus by fluorescent in situ hybridization. The results showed that the neuropeptides were widely distributed, especially in sensory and neuroendocrine brain regions. In the hypothalamic lateral tuberal nucleus, the putative homolog to the mammalian arcuate nucleus, npya, agrp1, cart2b, and pomca were predominantly localized in distinct neurons; however, some neurons coexpressed cart2b/pomca. This is the first demonstration of coexpression of cart2b/pomca in the tuberal hypothalamus of a teleost. Collectively, our data suggest that the lateral tuberal nucleus is the center for appetite control in salmon, similar to that of mammals. Extrahypothalamic brain regions might also be involved in regulating food intake, including the olfactory bulb, telencephalon, midbrain, and hindbrain.

Expression of leptin receptor gene in developing and adult zebrafish

Interactions of leptin and leptin receptors play crucial roles during animal development and regulation of appetite and energy balance. In this study we analyzed expression pattern of a zebrafish leptin receptor gene in both developing and adult zebrafish using in situ hybridization and Q-PCR methods. Zebrafish leptin receptor message ( lepr) was detected in all embryonic and larval stages examined, and in adult zebrafish. In embryonic zebrafish, lepr was mainly expressed in the notochord. As development proceeded, lepr expression in the notochord decreased, while its expression in several other tissues, including the trunk muscles and gut, became evident. In both larval and adult brains, large lepr expressing cells were detected in similar regions of the hindbrain. In adult zebrafish, lepr expression was also observed in several other brain regions including the hypothalamic lateral tuberal nucleus, the fish homolog of the arcuate nucleus. Q-PCR experiments confirmed lepr expression in the adult fish brain, and also showed lepr expression in several adult tissues including liver, muscle and gonads. Our results showed that lepr expression was both spatially and temporally regulated.

Endogenous melanocortin antagonist in fish: structure, brain mapping, and regulation by fasting of the goldfish agouti-related protein gene.

Agouti-related protein (AGRP) is a naturally occurring antagonist of melanocortin. In mammals, central AGRP expression is restricted to the arcuate nucleus in which it plays a key role in the control of energy balance by antagonizing melanocortin effects at melanocortin 4 receptors. In goldfish, melanocortin 4 receptor is profusely expressed within the main brain areas for the control of energy balance, and central administration of agonist or antagonist analogs inhibits or stimulates food intake, respectively. Here we demonstrate that the goldfish genome has a homologous gene to mammalian AGRP. Detailed brain mapping by in situ hybridization shows that AGRP is exclusively expressed in the ventrobasal hypothalamic lateral tuberal nucleus, the teleostean homolog of the arcuate nucleus. Fasting up-regulates its mRNA levels in the lateral tuberal nucleus. In the periphery, AGRP is expressed in several tissues including ovary, muscle, and ventral skin, suggesting that AGRP might regulate peripheral actions of melanocortin peptides. The results provide the first evidence for an endogenous melanocortin antagonist in nontetrapod species and suggest that hypothalamic overexpression during fasting might regulate the inhibitory effects of melanocortin peptides on food intake in goldfish.

Argyrophilic grain disease: frequency of occurrence in different age categories and neuropathological diagnostic criteria.

Argyrophilic grain disease is a progressive degenerative disorder of the human brain which becomes increasingly prevalent with advancing age. The disease entails multiple neuronal systems and results from cytoskeletal degeneration in only a few neuronal types and in oligodendrocytes. Immunoreactions for abnormally phosphorylated tau protein permit identification of the changes. Only a fraction of the emerging abnormal fibrillary material shows a pronounced argyrophilia. Essential for neuropathological diagnosis is assessment of the presence of small spindle-shaped argyrophilic grains in neuronal processes. The anteromedial portion of the temporal lobe bears the brunt of the lesions. Grains generally can be found in abundance in the entorhinal region, the first Ammon's horn sector, the subcortical nuclear complex of the amygdala, and the hypothalamic lateral tuberal nucleus. Frequently, the lesions co-exist with those typically found in Alzheimer's disease or other tauopathies. Owing to the characteristic grains, the disorder easily can be differentiated from other tauopathies. 2661 non-selected brains obtained at autopsy included 125 cases of argyrophilic grain disease (5%) from individuals between 51 and 96 years of age (mean 79 years) . The fact that the same material contained 146 cases of fully developed Alzheimer's disease (6%) supports the view that argyrophilic grain disease is not a rare disorder. Its prevalence with and without concomitant neurofibrillary changes of the Alzheimer type grows with increasing age. Argyrophilic grain disease merits attention because of its frequent occurrence and its potential to cause severe brain dysfunction.

Pick's disease: cytoskeletal changes in the hypothalamic lateral tuberal nucleus

Basolateral portions of the human hypothalamus contain an extended nuclear gray, the lateral tuberal nucleus (LTN), which undergoes conspicuous pathological changes in a number of neurodegenerative diseases. The present study points to the severe affliction of this nucleus in Pick's disease (PID). Immunoreactions for abnormally phosphorylated tau-protein permit identification of the permutations. Only a fraction of the abnormal fibrillary material developing in the course of the disease shows a pronounced argyrophilia. Key features are the Pick bodies (PBs) which contain an argyrophilic material. Unusual non-spherical PBs develop in the LTN as flat structures with peripheral indentations. Small teardrop-like Pick neurites (PNs) emerge in varicose widenings of neuronal processes and display a much weaker argyrophilia. The characteristic alterations seen in PID reliably can be differentiated from lesions of the LTN which slowly emerge in the course of Alzheimer's disease (AD).

Somatostatin 1–12 immunoreactivity is decreased in the hypothalamic lateral tuberal nucleus of Huntington's disease patients

The hypothalamic lateral tuberal nucleus (NTL) can be recognized in man and higher primates, only. The function of this nucleus is unknown, but the NTL is affected in a variety of human neurodegenerative diseases, including Huntington's disease (HD) and Alzheimer's disease. In the present study we demonstrate an abundant presence of somatostatin 1–12 (SSTI-12) immunoreactivity in both neurites and perikarya of the NTL. This immunoreactivity could be visualized best after microwave pretreatment. In HD brains, NTL SSTI-12 immunoreactivity was greatly reduced, providing further evidence of the presence of SSTI-12 as an intrinsic neuropeptide in the NTL. Although striatal SST neurons escape destruction in HD, our study demonstrates that not all SST neurons are resistant to the degenerative process in this disease.

Somatostatin 1–12 immunoreactivity is decreased in the hypothalamic lateral tuberal nucleus of Huntington's disease patients

The hypothalamic lateral tuberal nucleus (NTL) can be recognized in man and higher primates, only. The function of this nucleus is unknown, but the NTL is affected in a variety of human neurodegenerative diseases, including Huntington's disease (HD) and Alzheimer's disease. In the present study we demonstrate an abundant presence of somatostatin 1–12 (SSTI-12) immunoreactivity in both neurites and perikarya of the NTL. This immunoreactivity could be visualized best after microwave pretreatment. In HD brains, NTL SSTI-12 immunoreactivity was greatly reduced, providing further evidence of the presence of SSTI-12 as an intrinsic neuropeptide in the NTL. Although striatal SST neurons escape destruction in HD, our study demonstrates that not all SST neurons are resistant to the degenerative process in this disease.

AMPA and NMDA binding sites in the hypothalamic lateral tuberal nucleus: implications for Huntington's disease.

The excitatory amino acid (EAA) hypothesis of neuronal loss in Huntington's disease predicts that structures that show neuronal loss and gliosis will contain receptor-bearing neurons. In accordance with this hypothesis, the hypothalamic lateral tuberal nucleus, severely affected in Huntington's disease, showed a high density of NMDA and AMPA binding sites in four normal subjects.

Chapter 17 The hypothalamic lateral tuberal nucleus: normal anatomy and changes in neurological diseases

The lateral tuberal nucleus is a circumscribed cell mass in the lateral posterior part of the hypothalamus, containing about 60000 neurons. It can be recognized in man and higher primates, probably not in other mammals. Its neurotransmitter content and connections with other parts of the brain are as yet unknown. But receptors for corticotropin-releasing factor and somatostatin, as well as muscarinic cholinergic receptors, benzodiazepine receptors and N-methyl-D-aspartate receptors have been localized within the confines of the nucleus. The lateral tuberal nucleus is affected in a number of human neurodegenerative diseases. Changes in Parkinson's disease are the least obvious: Lewy bodies appear in small amounts, the majority of them apparently lying outside a neuronal perikaryon. Neuronal loss does not occur. In Alzheimer's disease the number of neurons seems to be normal as well. Rarely silver staining tangles occur, and the deposition of A4/beta-protein in amorphous plaques is moderate. Yet, NTL neurons stain heavily in Alz-50 immunocytochemistry, while Alz-50 staining in NTL neurites is very dense. These changes are interpreted as indicating early Alzheimer-related pathology. In Huntington's disease the NTL loses neurons. This loss is related to the severity of the disease: patients who first display motor disturbances at an early age will lose more neurons than those who start later. The relation between these clinical characteristics and the severity of neuronal loss is such, that it seems likely that NTL neurons possess a special vulnerability for the effect of the Huntington gene. This could be related to their NMDA-receptor content. It is hypothesized that the NTL is involved in a neuronal network that regulates feeding and metabolism. NTL pathology may explain the peculiar catabolic state of many patients with Alzheimer's or Huntington's diseases.

The hypothalamic lateral tuberal nucleus and the characteristics of neuronal loss in Huntington's disease

Neurons in the hypothalamic lateral tuberal nucleus (NTL) were counted in 16 Huntington's disease (HD) patients and 12 controls. The control range was 47,500–71,700. In the HD cases the number ranged from 2,800 to 40,600. The log-transformed counts of the HD patients correlated closely with age-at-death ( r = 0.66, P < 0.01) and age-at-onset ( r = 0.78, P < 0.001), but not with duration of disease, nor with the severity of the neostriatal changes. Because of its vulnerability to the effects of the HD gene and its simplicity, the NTL seems fit to study the characteristics of neuronal death in HD.

The hypothalamic lateral tuberal nucleus in Alzheimer's disease

The hypothalamic lateral tuberal nucleus was investigated in 5 young patients, aged 45 to 64 years, with Alzheimer's disease (AD) and in 5 age-matched control subjects. Combining conventional histopathological and immunocytochemical staining with neuronal counts, a peculiar form of neuronal pathology was characterized. Although neurons and neurites in the lateral tuberal nucleus of AD specimens were heavily stained by Alz-50, silver and thioflavine-S stains disclosed few neurofibrillary tangles or neurites. The numbers of neurons in the lateral tuberal nucleus of patients with AD (67,450; SEM = 5,050) were no different from those of control subjects (58,900; SEM = 2,450). In the AD patients, few plaques were present and were almost exclusively of the amorphous variety. We conclude that neurons in the lateral tuberal nucleus show an early stage of AD-related cytoskeletal pathology (Alz-50 positivity), but without plaques or neuronal death.

Atrophy of the Hypothalamic Lateral Tuberal Nucleus in Huntingtonʼs Disease

The hypothalamic lateral tuberal nucleus (NTL) was studied in the formalin-fixed brains of five patients with Huntington's disease (HD) and in five age- and sex-matched controls. With the Klüver-Barrera (luxol fast blue/cresyl violet) and hematoxylin and eosin stains the NTL was defined by its cytoarchitectonic characteristics. The nucleus was composed of one type of neuron and had about 60,000 cells. In HD, up to 90% neuronal loss was found in the NTL. The remaining neurons showed features of degeneration and there was astrocytosis. The estimated total number of glial cells in the NTL was reduced to 80% of the control values, which was exclusively accounted for by a reduction of 40% in the number of oligodendrocytes. The total number of astrocytes was unchanged. Grouping of astrocytes and the changes observed in glial fibrillary acidic protein immunocytochemistry suggested that astrocytic proliferation occurred.

CORTICAL AND SUBCORTICAL ARGYROPHILIC GRAINS CHARACTERIZE A DISEASE ASSOCIATED WITH ADULT ONSET DEMENTIA

Unusual cytoskeleton abnormalities were found in the brains of 28 individuals afflicted with adult onset dementia. Most conspicuous were small spindle-shaped argyrophilic grains loosely scattered throughout the neuropil. Additionally, coiled bodies of silver-stained filaments were encountered, mainly located within the white matter close to the cortical grey matter. Argyrophilic grains and coiled bodies contained dense accumulations of straight filaments with a diameter of about 9 nm. The argyrophilic grains were found in abundance within sector CA1 of the Ammon's horn and layer Pre-beta of the entorhinal region. A slightly less dense scattering of the grains occurred in layer IIIab of the adjoining temporal isocortex, insular cortex and orbitofrontal cortex. The basolateral amygdaloid complex and the hypothalamic lateral tuberal nucleus were the most affected subcortical structures. Deeper brain stem nuclei merely showed a sparse number of grains or were devoid of them. Eighty brains of demented individuals were examined. Forty-eight of them showed the features of Alzheimer's disease and four showed the features of Pick's disease. Twenty-eight cases revealed the abnormalities under consideration. Ten showed exclusively argyrophilic grains and coiled bodies, while 16 also had neuritic plaques, neurofibrillary tangles, and neuropil threads. One of the 28 cases was associated with Parkinson's disease and one showed features of both Parkinson's and Alzheimer's disease. Twenty brains of non-demented individuals of about the same age and devoid or almost devoid of Alzheimer changes were used as controls. None of the control brains showed the presence of argyrophilic grains and coiled bodies. These changes, therefore, are considered the morphological substrate of an unknown disease associated with adult onset dementia.