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1.
Neurochem Res ; 46(4): 853-865, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33439431

RESUMO

The A11 region plays a role in numerous physiological functions, including pain and locomotor activity, and consists of a variety of neurons including GABAergic, calbindin positive (Calb+), and dopaminergic (DA) neurons. However, the neurochemical nature of Calb+ neurons and their regulatory role in the A11 region remain largely unknown. In this study, we examined the kind of functional markers co-expressed in the Calb+ neurons using sections from 8-week-old rats. To examine a marker related to classical neurotransmitters, we performed in situ hybridization for vesicular glutamate transporter 2 (vGluT2) or glutamate decarboxylase (GAD) 65 and 67, in conjunction with Calb immunohistochemistry. We found cellular co-expression of Calb with vGluT2 or GAD65/67 throughout the A11 region. Nearly all Calb+/GAD65/67+ neurons were found in the rostral-middle aspect of the A11 region. In contrast, Calb+/vGluT2+ neurons were found predominantly in the middle-caudal aspect of the A11 region. For receptors and neuropeptides, we performed immunohistochemistry for androgen receptor (AR), estrogen receptors (ERα and ERß), and calcitonin gene-related peptide (CGRP). We found that Calb+ neurons co-expressed AR in the rostral aspect of the A11 region in both male and female rats. However, we rarely find cellular co-expression of Calb with ERα or ERß in this region. For CGRP, we found both Calb+ neurons with or without CGRP expression. These results demonstrate that Calb+ neurons co-express many functional markers. Calb+ neurons have a distinct distribution pattern and may play a variety of regulatory roles, depending on their location within the A11 region.


Assuntos
Encéfalo/metabolismo , Calbindinas/metabolismo , Neurônios/metabolismo , Animais , Encéfalo/citologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Glutamato Descarboxilase/metabolismo , Masculino , Ratos Sprague-Dawley , Receptores Androgênicos/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
2.
PLoS One ; 16(1): e0245615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33449938

RESUMO

This study aimed to provide the performance, localization and expression of the epithelial calcium transporter channels Calbindin-D28k (Calb) and TRPV6, and of the morphology of the digestive and reproductive system of laying quail under heat stress (HS), and with methionine supplementation (MS). This study characterized the positivity (immunohistochemistry) and expression (real-time PCR) of calcium channels in the kidneys, intestine and uterus of 504 laying quails under different MS (100, 110 and 120%) and temperatures (20, 24, 28 and 32°C). The animals under HS (32°C) had lower villus height, villus:crypt ratio, and goblet cell index in the duodenum and jejunum, fewer secondary and tertiary uterine folds, smaller hepatic steatosis, and increased number of distal convoluted renal tubules (CT) positive to Calb, and increased positivity in proximal CTs. Deleterious effects of HS were minimized with MS for: duodenal crypts, number of goblet cells of the jejunum, number of uterine folds, decreased Calb positivity in intestines and kidney, increased positivity of Calb in the uterus and increased TRPV6 gene expression in the kidney (P≤0.05). Epithelial calcium transporters were altered due to less need for calcium absorption and reabsorption due to more calcium available with the MS, increasing egg production in HS and quality in termoneutrality (P≤0.05). MS further increased intestinal villus absorption area and height, increased steatosis, decreased Calb positivity in the intestine and kidney, increased uterine positivity of Calb, and increase Calb and TRPV6 expression in the kidney (P≤0.001) under thermoneutrality. It was concluded that the use of MS (120%) is justifiable in order to partially reverse the deleterious effects of HS on the production, in the epithelial calcium carriers, and in the digestory and reproductive morphology of laying quail.


Assuntos
Proteínas Aviárias/biossíntese , Calbindinas/biossíntese , Duodeno , Regulação da Expressão Gênica/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Fígado , Metionina/farmacologia , Codorniz , Canais de Cátion TRPV/biossíntese , Útero , Animais , Duodeno/anatomia & histologia , Duodeno/metabolismo , Feminino , Fígado/anatomia & histologia , Fígado/metabolismo , Codorniz/anatomia & histologia , Codorniz/metabolismo , Útero/anatomia & histologia , Útero/metabolismo
3.
J Chem Neuroanat ; 112: 101914, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33388377

RESUMO

The location and distribution of the calcium-binding protein calbindin-D28k (CB) has been considered to be of great value as a neuronal marker for identifying distinct brain regions and discrete neuronal populations. In the amygdaloid complex (AC), the balance of excitatory and inhibitory inputs is controlled by CB immunoreactive interneurons. Alterations of inhibitory mechanisms in the AC may play a role in the emotional symptomatology of neurological diseases like Alzheimer's and psychiatric disorders like posttraumatic stress disorder. The present investigation examined the distribution and morphology of CB-containing neurons, neuropils and fibers in marmoset monkey ACs by using immunohistochemical and morphometrical methods. We recognized four types of CB cells in the AC: type 1 (multipolar), type 2 (spherical or bipolar), type 3 (pyramidal) and type 4 (halo cells), a cell type specific to the marmoset located in the basal and central nuclei. We detected CB cells in all nuclei and areas of the AC, where most of the cells were present in the deep nuclei (lateral, basal, accessory basal and paralaminar). In the superficial nuclei (the nucleus of the lateral olfactory tract, medial nucleus, periamygdaloid cortex and cortical nuclei), the CB cells were abundant in layers 2 and 3. The intercalated nuclei contained small densely packed cells. The CB neuropils were particularly dense in layer 1 of the superficial nuclei, in the deep nuclei and in the amygdalohippocampal area. Large CB immunoreactive neurons in the white matter and fibers with varicosities were found in the myelin tracts that surrounded the AC. These findings are the first step in determining whether some of these cells are specifically disrupted in pathological states.


Assuntos
Tonsila do Cerebelo/metabolismo , Calbindinas/metabolismo , Neurônios/metabolismo , Tonsila do Cerebelo/citologia , Animais , Callithrix , Feminino , Masculino , Fibras Nervosas/metabolismo , Neurônios/citologia , Parvalbuminas/metabolismo
4.
Angew Chem Int Ed Engl ; 60(16): 8851-8858, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33480463

RESUMO

Calbistrins are fungal polyketides consisting of the characteristic decalin and polyene moieties. Although the biosynthetic gene cluster of calbistrin A was recently identified, the pathway of calbistrin A biosynthesis has largely remained uninvestigated. Herein, we investigated the mechanism by which the backbone structures of calbistrins are formed, by heterologous and in vitro reconstitution of the biosynthesis and a structural biological study. Intriguingly, our analyses revealed that the decalin and polyene portions of calbistrins are synthesized by the single polyketide synthase (PKS) CalA, with the aid of the trans-acting enoylreductase CalK and the trans-acting C-methyltransferase CalH, respectively. We also determined that the esterification of the two polyketide parts is catalyzed by the acyltransferase CalD. Our study has uncovered a novel dual-functional PKS and thus broadened our understanding of how fungi synthesize diverse polyketide natural products.


Assuntos
Produtos Biológicos/metabolismo , Calbindinas/biossíntese , Policetídeo Sintases/metabolismo , Aspergillus/enzimologia , Produtos Biológicos/química , Calbindinas/química , Estrutura Molecular
5.
Mol Neurobiol ; 58(5): 1952-1962, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33411242

RESUMO

Neurogenesis in the dentate gyrus (DG) of the adult hippocampus is actively involved in brain homeostasis. Thus, identification of novel regulators in adult neurogenesis could significantly contribute to new therapies. We have recently unraveled the regulatory role of NR5A2 (also known as LRH1), a druggable orphan nuclear receptor, in embryonic neurogenesis. However, its involvement in adult neurogenesis is still an open question. Here we show that NR5A2 is differentially expressed in the DG of the adult hippocampus with neurons exhibiting higher levels of expression than adult neural stem/progenitor cells (aNSCs), suggesting a correlation with neuronal differentiation. Notably, NR5A2 overexpression in ex vivo cultured aNSCs induces expression of Prox1, a critical regulator of adult hippocampal neurogenesis. In agreement, NR5A2 is sufficient to reduce proliferation, increase neuronal differentiation, and promote axon outgrowth. Moreover, depletion of NR5A2 in DG cells in vivo caused a decrease in the number of NeuN as well as Calbindin-positive neurons, indicating its necessity for the maintenance of neuronal identity. Our data propose a regulatory role of NR5A2 in neuronal differentiation and fate specification of adult hippocampal NSCs.


Assuntos
Hipocampo/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Neurônios/metabolismo , Animais , Calbindinas/metabolismo , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Camundongos
6.
Anat Rec (Hoboken) ; 304(5): 1094-1104, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33040447

RESUMO

The hypothalamus is involved in the regulation of rhythms, autonomic, endocrine, and behavioral functions and may also participate in aging development and control. The aim of this work was to study the expression of calbindin (CB) and calretinin (CR) in the ventromedial (VMH) and dorsomedial (DMH) hypothalamic nuclei in young and old rats of both sexes by immunohistochemistry and western blotting. In young animals, the largest number of CB-immunoreactive (IR) neurons was detected in the ventral part of DMH (DMHv) and smaller percentage was found in its dorsal part (DMHd), in the dorsomedial part of the VMH (VMHdm) and in the ventrolateral part of the VMH (VMHvl). In aged animals, the percentage of CB-IR neurons significantly decreased in all studied nuclei, including DMHv, DMHd, VMHdm and VMHvl. CR-IR neurons were found in moderate number in the DMHv, DMHd, VMHdm and VMHvl of young rats. In aged rats, the percentage of CR-IR neurons significantly increased in the DMHv, DMHd, VMHdm and VMHvl. Less than one third of IR neurons colocalized CB and CR in young and aged rats. The expression of CB significantly decreased, and the expression of CR significantly increased in the DMH and VMH during aging by western blot analysis. Thus, there are opposite changes of the calcium-binding proteins expression in the hypothalamic nuclei involved in the metabolic and sexual regulation during aging.


Assuntos
Envelhecimento/metabolismo , Calbindina 2/metabolismo , Calbindinas/metabolismo , Núcleo Hipotalâmico Dorsomedial/metabolismo , Núcleo Hipotalâmico Ventromedial/metabolismo , Animais , Feminino , Masculino , Neurônios/metabolismo , Ratos
7.
Anat Rec (Hoboken) ; 304(5): 1105-1118, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33119932

RESUMO

The visual system of cetaceans is at best poorly understood. With a handful of electrophysiological studies and a limited number of histological preparations from well-preserved specimen, the investigation of the principles underlying the cortical organization in cetaceans remains a challenge. In the course of our current investigation, we identified the transition from V2 to V1 in the long-finned pilot whale Globicephala melas, only recognizable through immunocytochemistry, and a similar if not homologue transition in the sheep Ovis aries. Our results emphasize the importance of differential pattern recognition in which the application of different markers uncovers a diversity in a delphinid's cortex, formerly widely considered as uniform and archetypal. In fact, the evidence that we present suggests the existence of relatively unacknowledged areas beyond the well-known sensory territories in cetaceans.


Assuntos
Córtex Visual/metabolismo , Animais , Calbindina 2/metabolismo , Calbindinas/metabolismo , Ovinos , Baleias Piloto
8.
Exp Anim ; 70(1): 137-143, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33115988

RESUMO

Noda epileptic rat (NER) is a mutant model for epilepsy that exhibits spontaneous generalized tonic-clonic seizure. Epileptogenesis of NER remains to be elucidated; but it is detected an insertion of an endogenous retrovirus sequence in intron 2 of the PHD finger protein 24 (Phf24) gene, encoding Gαi-interacting protein (GINIP). Phf24 is a strong candidate gene for epileptogenesis in NER. PHF24 modulates GABAB signaling through interacting with Gαi protein. To clarify the epileptogenesis of NER, we investigated a distribution of PHF24-expressing cells in the central nerve system (CNS). While broad expression of PHF24 was observed in the CNS, characteristic expression was noted in the periglomerular layer of the olfactory bulb and the lamina II of the spinal cord in the control rats. These cells showed co-expression with calbindin or calretinin, inhibitory interneuron markers. In the olfactory bulb, 15.6% and 41.2% of PHF24-positive neurons co-expressed calbindin and calretinin, respectively. Immunoelectron microscopy revealed that PHF24 was located in the presynaptic terminals, synaptic membranes and cytoplasmic matrix of neuronal soma. Our data suggested PHF24 is expressed in the inhibitory interneurons and may play important roles in modulation of the GABAB signaling.


Assuntos
Expressão Gênica , Estudos de Associação Genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Interneurônios/metabolismo , Convulsões/genética , Convulsões/metabolismo , Animais , Calbindina 2/metabolismo , Calbindinas/metabolismo , Sistema Nervoso Central/citologia , Sistema Nervoso Central/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Bulbo Olfatório/metabolismo , Ratos Endogâmicos F344 , Transdução de Sinais/genética , Medula Espinal/metabolismo , Ácido gama-Aminobutírico/metabolismo
9.
J Anat ; 238(1): 1-12, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32885430

RESUMO

The present study analyses the organization and selected neurochemical features of the claustrum and visual cortex of the sheep, based on the patterns of calcium-binding proteins expression. Connections of the claustrum with the visual cortex have been studied by tractography. Parvalbumin-immunoreactive (PV-ir) and Calbindin-immunoreactive (CB-ir) cell bodies increased along the rostro-caudal axis of the nucleus. Calretinin (CR)-labeled somata were few and evenly distributed along the rostro-caudal axis. PV and CB distribution in the visual cortex was characterized by larger round and multipolar cells for PV, and more bitufted neurons for CB. The staining pattern for PV was the opposite of that of CR, which showed densely stained but rare cell bodies. Tractography shows the existence of connections with the caudal visual cortex. However, we detected no contralateral projection in the visuo-claustral interconnections. Since sheep and goats have laterally placed eyes and a limited binocular vision, the absence of contralateral projections could be of prime importance if confirmed by other studies, to rule out the role of the claustrum in stereopsis.


Assuntos
Claustrum/anatomia & histologia , Neurônios/metabolismo , Ovinos/anatomia & histologia , Córtex Visual/anatomia & histologia , Animais , Calbindina 2/metabolismo , Calbindinas/metabolismo , Claustrum/metabolismo , Feminino , Vias Neurais/anatomia & histologia , Vias Neurais/metabolismo , Parvalbuminas/metabolismo , Córtex Visual/metabolismo
10.
Eur J Neurosci ; 54(5): 5815-5833, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33278847

RESUMO

Emerging evidence suggests functional roles for microglia in the healthy, mature nervous system. However, we know little of the cellular density and ramified morphology of microglia in sensory systems, and even less of their inter-relationship with inhibitory neurons. We therefore conducted fluorescent multi-channel immunohistochemistry and confocal microscopy in guinea pigs of both sexes for Iba1, GAD67, GFAP, calbindin, and calretinin. We explored these markers in the inferior colliculi (IC), which contain sub-regions specialized for different aspects of auditory processing. First, we found that while the density of Iba1+ somata is similar throughout the IC parenchyma, Iba1+ microglia in dorsal cortex are significantly more ramified than those in the central nucleus or lateral cortex. Conversely, Iba1+ ramifications in ventral central nucleus, a region with the highest density of GAD67+ (putative GABAergic) neurons in IC, are longer with fewer ramifications. Second, we observed extensive abutments of ramified Iba1+ processes onto GAD67+ somata throughout the whole IC and developed novel measures to quantify these. Cluster analyses revealed two novel sub-types of GAD67+ neuron that differ in the quantity of Iba1+ somatic abutments they receive. Unlike previous classification schemes for GAD67+ neurons in IC, these clusters are not related to GAD67+ soma size. Taken together, these data demonstrate that microglial ramifications vary between IC sub-regions in the healthy, adult IC, possibly related to the ongoing demands of their niche. Furthermore, Iba1+ abutments onto neuronal somata are a novel means by which GAD67+ neurons can be classified.


Assuntos
Colículos Inferiores , Animais , Calbindinas , Feminino , Neurônios GABAérgicos , Cobaias , Imuno-Histoquímica , Masculino , Microglia
11.
Neuroscience ; 455: 113-127, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33359654

RESUMO

Inhibitory circuits in the basolateral nuclear complex of the amygdala (BNC) critical for controlling the acquisition, expression, and extinction of emotional responses are mediated by GABAergic interneurons (INs). Studies in rodents have demonstrated that separate IN subpopulations, identified by their expression of calcium-binding proteins and neuropeptides, play discrete roles in the intrinsic circuitry of the BNC. Far less is known about IN subpopulations in primates. In order to fill in this gap in our understanding of primate INs, the present investigation used dual-labeling immunohistochemistry for IN markers to identify subpopulations expressing cholecystokinin (CCK), calbindin (CB), calretinin (CR), and somatostatin (SOM) in somata and axon terminals in the monkey BNC. In general, colocalization patterns seen in somata and axon terminals were similar. It was found that there was virtually no colocalization of CB and CR, the two calcium-binding proteins investigated. Three subtypes of CCK-immunoreactive (CCK+) INs were identified on the basis of their expression of CR or CB: (1) CCK+/CR+; (2) CCK+/CB+); and (3) CCK+/CR-/CB-. Almost no colocalization of CCK with SOM was observed, but there was extensive colocalization of SOM and CB. CCK+, CR+, and CCK+/CR+ double-labeled axon terminals were seen surrounding pyramidal cell somata in basket-like plexuses, as well as in the neuropil. CB+, SOM+, and CB+/SOM+ terminals did not form baskets, suggesting that these IN subpopulations are mainly dendrite-targeting neurons. In general, the IN subpopulations in the monkey are not dissimilar to those seen in rodents but, unlike rodents, CB+ INs in the monkey are not basket cells.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Interneurônios , Animais , Complexo Nuclear Basolateral da Amígdala/metabolismo , Calbindina 2 , Calbindinas , Feminino , Interneurônios/metabolismo , Macaca mulatta , Masculino , Parvalbuminas/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo
12.
Mol Neurobiol ; 58(1): 348-361, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32939692

RESUMO

Negative urgency is a facet of impulsivity associated with negative affect and risky behavior that may involve the amygdala. The current study determined if social isolation during development alters negative urgency and c-Fos activity in the basolateral amygdala (BLA). Female Sprague-Dawley rats were raised in an isolated condition (IC), a standard social condition (SC), or an enriched condition (EC) and then were tested for locomotor activity, novelty place preference, and negative urgency using a reward omission task. Following performance on the reward omission task, the brains were analyzed for c-Fos expression in Ca2+/calmodulin kinase II (CaMKII) and calbindin (CB) neurons, as well as in parvalbumin (PV) neurons associated with perineuronal nets (PNNs) in BLA. IC rats exhibited enhanced locomotion compared with both SC and EC rats, as well as enhanced novelty place preference compared with EC rats; only IC rats showed increased responding following omission of an expected reward (negative urgency). Following completion of the reward omission task, IC rats also displayed increased percent of c-Fos neurons in BLA associated with CaMKII, CB, and PV neurons compared with SC and EC rats. In IC rats, c-Fos activation in BLA occurred following the omission of an expected reward. Finally, IC rats displayed reduced PNN intensity associated with PV neurons compared with EC rats, but the percent of these neurons co-expressing c-Fos was greater in IC rats; SC rats were intermediate between IC and EC rats. Negative urgency was observed in IC rats, but not SC or EC rats. While multiple mechanisms are likely involved, this behavioral effect was associated with an isolation-induced increase in activity of excitatory neurons in BLA, as well as decreased PNN intensity surrounding GABAergic neurons in the same region.


Assuntos
Tonsila do Cerebelo/patologia , Rede Nervosa/patologia , Recompensa , Isolamento Social , Análise e Desempenho de Tarefas , Animais , Calbindinas/metabolismo , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Feminino , Locomoção , Neurônios/patologia , Parvalbuminas/metabolismo , Fenótipo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Sprague-Dawley
13.
Sci Rep ; 10(1): 20108, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208843

RESUMO

Protein folding is governed by non-covalent interactions under the benefits and constraints of the covalent linkage of the backbone chain. In the current work we investigate the influence of loop length variation on the free energies of folding and ligand binding in a small globular single-domain protein containing two EF-hand subdomains-calbindin D9k. We introduce a linker extension between the subdomains and vary its length between 1 to 16 glycine residues. We find a close to linear relationship between the linker length and the free energy of folding of the Ca2+-free protein. In contrast, the linker length has only a marginal effect on the Ca2+ affinity and cooperativity. The variant with a single-glycine extension displays slightly increased Ca2+ affinity, suggesting that the slightly extended linker allows optimized packing of the Ca2+-bound state. For the extreme case of disconnected subdomains, Ca2+ binding becomes coupled to folding and assembly. Still, a high affinity between the EF-hands causes the non-covalent pair to retain a relatively high apparent Ca2+ affinity. Our results imply that loop length variation could be an evolutionary option for modulating properties such as protein stability and turnover without compromising the energetics of the specific function of the protein.


Assuntos
Calbindinas/química , Calbindinas/metabolismo , Animais , Calbindinas/genética , Cálcio/metabolismo , Varredura Diferencial de Calorimetria , Gatos , Motivos EF Hand , Ligantes , Conformação Proteica , Desnaturação Proteica , Dobramento de Proteína , Estabilidade Proteica , Termodinâmica
14.
Vet Pathol ; 57(6): 889-914, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021158

RESUMO

Pigs are considered one of the relevant animal models for ocular research as they share several histological and anatomical similarities with the human eye. With the increasing interest in juvenile animal models, this study aimed to describe the postnatal development of ocular structures in 16 Göttingen minipigs and 25 F2 domestic pigs, between birth and 6 months of age, using histopathology and immunohistochemistry against Ki-67, caspase-3, calbindin, glial fibrillary acidic protein, rhodopsin, and synaptophysin. All ocular structures in both pig breeds were incompletely developed at birth and for variable periods postnatally. Noteworthy histological features of immaturity included vascularization in the corneal stroma in neonatal Göttingen minipigs, increased cellularity in different substructures, remnants of the hyaloid vasculature, short and poorly ramified ciliary body processes, and a poorly developed cone inner segment. Increased cellular proliferation, highlighted by abundant Ki-67 immunolabeling, was observed in almost all developing structures of the pig eye for variable periods postnatally. Apoptosis, highlighted with caspase-3 immunolabeling, was observed in the retinal inner nuclear layer at birth and in the regressing hyaloid vasculature remnants. Immunohistochemistry against rhodopsin, synaptophysin, and calbindin demonstrated the short size of the developing photoreceptors and the immature cone inner segment morphology. Calbindin labeling revealed significant differences in the amount of positively labeled cone nuclei between the retinal area centralis and the non-area centralis regions. The elongation of Müller cell processes in the developing retina was shown with glial fibrillary acidic protein. In both pig breeds, the eyes reached histomorphological and immunohistochemical maturity at 6 months of age.


Assuntos
Corpo Ciliar , Retina , Porco Miniatura , Animais , Calbindinas , Imuno-Histoquímica , Retina/crescimento & desenvolvimento , Suínos , Porco Miniatura/crescimento & desenvolvimento
15.
J Chem Neuroanat ; 110: 101873, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33086098

RESUMO

Here we report the unusual presence of thalamic reticular neurons immunoreactive for tyrosine hydroxylase in equids. The diencephalons of one adult male of four equid species, domestic donkey (Equus africanus asinus), domestic horse (Equus caballus), Cape mountain zebra (Equus zebra zebra) and plains zebra (Equus quagga), were sectioned in a coronal plane with series of sections stained for Nissl substance, myelin, or immunostained for tyrosine hydroxylase, and the calcium-binding proteins parvalbumin, calbindin and calretinin. In all equid species studied the thalamic reticular nucleus was observed as a sheet of neurons surrounding the rostral, lateral and ventral portions of the nuclear mass of the dorsal thalamus. In addition, these thalamic reticular neurons were immunopositive for parvalbumin, but immunonegative for calbindin and calretinin. Moreover, the thalamic reticular neurons in the equids studied were also immunopositive for tyrosine hydroxylase. Throughout the grey matter of the dorsal thalamus a terminal network also immunoreactive for tyrosine hydroxylase was present. Thus, the equid thalamic reticular neurons appear to provide a direct and novel potentially catecholaminergic innervation of the thalamic relay neurons. This finding is discussed in relation to the function of the thalamic reticular nucleus and the possible effect of a potentially novel catecholaminergic pathway on the neural activity of the thalamocortical loop.


Assuntos
Neurônios/metabolismo , Núcleos Talâmicos/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Calbindina 2/metabolismo , Calbindinas/metabolismo , Equidae , Masculino , Parvalbuminas/metabolismo
16.
Elife ; 92020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762844

RESUMO

Different subtypes of interneurons, destined for the olfactory bulb, are continuously generated by neural stem cells located in the ventricular and subventricular zones along the lateral forebrain ventricles of mice. Neuronal identity in the olfactory bulb depends on the existence of defined microdomains of pre-determined neural stem cells along the ventricle walls. The molecular mechanisms underlying positional identity of these neural stem cells are poorly understood. Here, we show that the transcription factor Vax1 controls the production of two specific neuronal subtypes. First, it is directly necessary to generate Calbindin expressing interneurons from ventro-lateral progenitors. Second, it represses the generation of dopaminergic neurons by dorsolateral progenitors through inhibition of Pax6 expression. We present data indicating that this repression occurs, at least in part, via activation of microRNA miR-7.


Assuntos
Regulação da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Células-Tronco Neurais/fisiologia , Neurogênese , Neuropeptídeos/metabolismo , Bulbo Olfatório/fisiologia , Fator de Transcrição PAX6/metabolismo , Animais , Calbindinas/genética , Diferenciação Celular , Feminino , Proteínas de Homeodomínio/genética , Masculino , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Neurais/classificação , Neuropeptídeos/genética , Fator de Transcrição PAX6/genética
17.
Brain Struct Funct ; 225(7): 2239-2269, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32743670

RESUMO

The organization of the pallial derivatives across vertebrates follows a comparable elementary arrangement, although not all of them possess a layered cortical structure as sophisticated as the cerebral cortex of mammals. However, its expansion along evolution has only been possible by the development and coevolution of the cellular networks formed by excitatory neurons and inhibitory interneurons. Thus, the comparative analysis of interneuron types in vertebrate models of key evolutionary significance will provide important information, due to the extraordinary anatomical sophistication of their interneuron systems with simpler behavioral implications. Particularly in mammals, the main consensus for classifying interneuron types is based on non-overlapping markers, which do not form a single population, but consist of several distinct classes of inhibitory cells showing co-expression of other markers. In our study, we analyzed immunohistochemically the expression of the main markers like somatostatin (SOM), parvalbumin (PV), calretinin (CR), calbindin (CB), neuropeptide Y (NPY) and/or nitric oxide synthase (NOS) at the pallial regions of three different models of Osteichthyes. First, we selected two tetrapods, one amniote from the genus Pseudemys belonging to the order Testudine, at the base of the amniote diversification and with a three-layered simple cortex, and the Anuran Xenopus laevis, an anamniote tetrapod with a non-layered evaginated pallium, and finally the order Polypteriform, a small fish group at the base of the actinopterygian diversification with an everted telencephalon. SOM was the most conserved interneuron type in terms of its distribution and co-expression with other markers such as CR, in contrast to PV, which showed a different pattern between the models analyzed. In addition, the SOM expression supports a homological relationship between the medial pallial derivatives in all the models. CR and CB expressions in the tetrapods were observed, particularly, CR expressing cells were detected in the medial and the dorsal pallial derivatives, in contrast to CB, which appeared only in discrete scattered populations. However, the pallium of Polypteriforms fishes was almost devoid of CR cells, in contrast to the important number of CB cells observed in all the pallial regions. The NPY immunoreactivity was detected in all the pallial domains of all the models, as well as cells coexpressing CR. Finally, the pallial nitrergic expression was also conserved, which allows to postulate the homological relationships between the ventropallial and the amygdaloid derivatives. In summary, even in basal pallial models the neurochemically characterized interneurons indicate that their first appearance took place before the common ancestor of amniotes. Thus, our results suggest a shared pattern of interneuron types in the pallium of all Osteichthyes.


Assuntos
Córtex Cerebral/metabolismo , Globo Pálido/metabolismo , Interneurônios/metabolismo , Animais , Calbindina 2/metabolismo , Calbindinas/metabolismo , Peixes , Neuropeptídeo Y/metabolismo , Óxido Nítrico Sintase/metabolismo , Parvalbuminas/metabolismo , Somatostatina/metabolismo
18.
Nature ; 583(7818): 813-818, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32699410

RESUMO

Most sensory information destined for the neocortex is relayed through the thalamus, where considerable transformation occurs1,2. One means of transformation involves interactions between excitatory thalamocortical neurons that carry data to the cortex and inhibitory neurons of the thalamic reticular nucleus (TRN) that regulate the flow of those data3-6. Although the importance of the TRN has long been recognised7-9, understanding of its cell types, their organization and their functional properties has lagged behind that of the thalamocortical systems they control. Here we address this by investigating the somatosensory and visual circuits of the TRN in mice. In the somatosensory TRN we observed two groups of genetically defined neurons that are topographically segregated and physiologically distinct, and that connect reciprocally with independent thalamocortical nuclei through dynamically divergent synapses. Calbindin-expressing cells-located in the central core-connect with the ventral posterior nucleus, the primary somatosensory thalamocortical relay. By contrast, somatostatin-expressing cells-which reside along the surrounding edges of the TRN-synapse with the posterior medial thalamic nucleus, a higher-order structure that carries both top-down and bottom-up information10-12. The two TRN cell groups process their inputs in pathway-specific ways. Synapses from the ventral posterior nucleus to central TRN cells transmit rapid excitatory currents that depress deeply during repetitive activity, driving phasic spike output. Synapses from the posterior medial thalamic nucleus to edge TRN cells evoke slower, less depressing excitatory currents that drive more persistent spiking. Differences in the intrinsic physiology of TRN cell types, including state-dependent bursting, contribute to these output dynamics. The processing specializations of these two somatosensory TRN subcircuits therefore appear to be tuned to the signals they carry-a primary central subcircuit tuned to discrete sensory events, and a higher-order edge subcircuit tuned to temporally distributed signals integrated from multiple sources. The structure and function of visual TRN subcircuits closely resemble those of the somatosensory TRN. These results provide insights into how subnetworks of TRN neurons may differentially process distinct classes of thalamic information.


Assuntos
Vias Neurais , Núcleos Talâmicos/citologia , Núcleos Talâmicos/fisiologia , Potenciais de Ação , Animais , Calbindinas/metabolismo , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Feminino , Cinética , Masculino , Camundongos , Inibição Neural , Neurônios/metabolismo , Somatostatina/metabolismo , Sinapses/metabolismo
19.
Elife ; 92020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32558643

RESUMO

Layering has been a long-appreciated feature of higher order mammalian brain structures but the extent to which it plays an instructive role in synaptic specification remains unknown. Here we examine the formation of synaptic circuitry under cellular heterotopia in hippocampal CA1, using a mouse model of the human neurodevelopmental disorder Type I Lissencephaly. We identify calbindin-expressing principal cells which are mispositioned under cellular heterotopia. Ectopic calbindin-expressing principal cells develop relatively normal morphological features and stunted intrinsic physiological features. Regarding network development, a connectivity preference for cholecystokinin-expressing interneurons to target calbindin-expressing principal cells is diminished. Moreover, in vitro gamma oscillatory activity is less synchronous across heterotopic bands and mutants are less responsive to pharmacological inhibition of cholecystokinin-containing interneurons. This study will aid not only in our understanding of how cellular networks form but highlight vulnerable cellular circuit motifs that might be generalized across disease states.


Assuntos
Calbindinas/metabolismo , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/fisiopatologia , Hipocampo/fisiopatologia , Interneurônios/fisiologia , Células Piramidais/fisiologia , Animais , Colecistocinina/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos
20.
Mol Neurobiol ; 57(8): 3439-3457, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32533466

RESUMO

Despite several compounds entering clinical trials for the negative and cognitive symptoms of schizophrenia, few have progressed beyond phase III. This is partly attributed to a need for improved preclinical models, to understand disease and enable predictive evaluation of novel therapeutics. To this end, one recent approach incorporates "dual-hit" neurodevelopmental insults like neonatal phencyclidine plus isolation rearing (PCP-Iso). Glutamatergic dysfunction contributes to schizophrenia pathophysiology and may represent a treatment target, so we used enzyme-based microsensors to evaluate basal- and drug-evoked glutamate release in hippocampal slices from rats that received neonatal PCP and/or isolation rearing. 5-HT6 antagonist-evoked glutamate release (thought to be mediated indirectly via GABAergic disinhibition) was reduced in PCP-Iso, as were cognitive effects of a 5-HT6 antagonist in a hippocampal glutamate-dependent novel object discrimination task. Yet mGlu7 antagonist-evoked glutamatergic and cognitive responses were spared. Immunohistochemical analyses suggest these findings (which mirror the apparent lack of clinical response to 5-HT6 antagonists in schizophrenia) are not due to reduced hippocampal 5-HT input in PCP-Iso, but may be explained by reduced calbindin expression. This calcium-binding protein is present in a subset of GABAergic interneurons receiving preferential 5-HT innervation and expressing 5-HT6 receptors. Its loss (in schizophrenia and PCP-Iso) would be expected to reduce interneuron firing and potentially prevent further 5-HT6 antagonist-mediated disinhibition, without impacting on responses of VIP-expressing interneurons to mGlu7 antagonism. This research highlights the importance of improved understanding for selection of appropriate preclinical models, especially where disease neurobiology impacts on cells mediating the effects of potential therapeutics.


Assuntos
Calbindinas/deficiência , Ácido Glutâmico/metabolismo , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Calbindinas/metabolismo , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fenciclidina/farmacologia , Receptores de Serotonina/efeitos dos fármacos , Serotonina/metabolismo
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