Neuroprotective and Regenerative Effects of Growth Hormone (GH) in the Embryonic Chicken Cerebral Pallium Exposed to Hypoxic-Ischemic (HI) Injury.

Prenatal hypoxic−ischemic (HI) injury inflicts severe damage on the developing brain provoked by a pathophysiological response that leads to neural structural lesions, synaptic loss, and neuronal death, which may result in a high risk of permanent neurological deficits or even newborn decease. It is known that growth hormone (GH) can act as a neurotrophic factor inducing neuroprotection, neurite growth, and synaptogenesis after HI injury. In this study we used the chicken embryo to develop both in vitro and in vivo models of prenatal HI injury in the cerebral pallium, which is the equivalent of brain cortex in mammals, to examine whether GH exerts neuroprotective and regenerative effects in this tissue and the putative mechanisms involved in these actions. For the in vitro experiments, pallial cell cultures obtained from chick embryos were incubated under HI conditions (<5% O2, 1 g/L glucose) for 24 h and treated with 10 nM GH, and then collected for analysis. For the in vivo experiments, chicken embryos (ED14) were injected in ovo with GH (2.25 µg), exposed to hypoxia (12% O2) for 6 h, and later the pallial tissue was obtained to perform the studies. Results show that GH exerted a clear anti-apoptotic effect and promoted cell survival and proliferation in HI-injured pallial neurons, in both in vitro and in vivo models. Neuroprotective actions of GH were associated with the activation of ERK1/2 and Bcl-2 signaling pathways. Remarkably, GH protected mature neurons that were particularly harmed by HI injury, but was also capable of stimulating neural precursors. In addition, GH stimulated restorative processes such as the number and length of neurite outgrowth and branching in HI-injured pallial neurons, and these effects were blocked by a specific GH antibody, thus indicating a direct action of GH. Furthermore, it was found that the local expression of several synaptogenic markers (NRXN1, NRXN3, GAP-43, and NLG1) and neurotrophic factors (GH, BDNF, NT-3, IGF-1, and BMP4) were increased after GH treatment during HI damage. Together, these results provide novel evidence supporting that GH exerts protective and restorative effects in brain pallium during prenatal HI injury, and these actions could be the result of a joint effect between GH and endogenous neurotrophic factors. Also, they encourage further research on the potential role of GH as a therapeutic complement in HI encephalopathy treatments.

A canonical interlaminar circuit in the sensory dorsal ventricular ridge of birds: The anatomical organization of the trigeminal pallium.

The dorsal ventricular ridge (DVR), which is the largest component of the avian pallium, contains discrete partitions receiving tectovisual, auditory, and trigeminal ascending projections. Recent studies have shown that the auditory and the tectovisual regions can be regarded as complexes composed of three highly interconnected layers: an internal senso-recipient one, an intermediate afferent/efferent one, and a more external re-entrant one. Cells located in homotopic positions in each of these layers are reciprocally linked by an interlaminar loop of axonal processes, forming columnar-like local circuits. Whether this type of organization also extends to the trigemino-recipient DVR is, at present, not known. This question is of interest, since afferents forming this sensory pathway, exceptional among amniotes, are not thalamic but rhombencephalic in origin. We investigated this question by placing minute injections of neural tracers into selected locations of vital slices of the chicken telencephalon. We found that neurons of the trigemino-recipient nucleus basorostralis pallii (Bas) establish reciprocal, columnar and homotopical projections with cells located in the overlying ventral mesopallium (MV). "Column-forming" axons originated in B and MV terminate also in the intermediate strip, the fronto-trigeminal nidopallium (NFT), in a restricted manner. We also found that the NFT and an internal partition of B originate substantial, coarse-topographic projections to the underlying portion of the lateral striatum. We conclude that all sensory areas of the DVR are organized according to a common neuroarchitectonic motif, which bears a striking resemblance to that of the radial/laminar intrinsic circuits of the sensory cortices of mammals.

Parallel organization of the avian sensorimotor arcopallium: Tectofugal visual pathway in the pigeon (Columba livia).

The sensory-motor division of the avian arcopallium receives parallel inputs from primary and high-order pallial areas of sensory and vocal control pathways, and sends a prominent descending projection to ascending and premotor, subpallial stages of these pathways. While this organization is well established for the auditory and trigeminal systems, the arcopallial subdivision related to the tectofugal visual system and its descending projection to the optic tectum (TeO) has been less investigated. In this study, we charted the arcopallial area displaying tectofugal visual responses and by injecting neural tracers, we traced its connectional anatomy. We found visual motion-sensitive responses in a central region of the dorsal (AD) and intermediate (AI) arcopallium, in between previously described auditory and trigeminal zones. Blocking the ascending tectofugal sensory output, canceled these visual responses in the arcopallium, verifying their tectofugal origin. Injecting PHA-L into the visual, but not into the auditory AI, revealed a massive projection to tectal layer 13 and other tectal related areas, sparing auditory, and trigeminal ones. Conversely, CTB injections restricted to TeO retrogradely labeled neurons confined to the visual AI. These results show that the AI zone receiving tectofugal inputs sends top-down modulations specifically directed to tectal targets, just like the auditory and trigeminal AI zones project back to their respective subpallial sensory and premotor areas, as found by previous studies. Therefore, the arcopallium seems to be organized in a parallel fashion, such that in spite of expected cross-modal integration, the different sensory-motor loops run through separate subdivisions of this structure.

The impact of gene expression analysis on evolving views of avian brain organization.

Recent studies have presented data on adult and developing avian brain organization. Jarvis et al. ([2013] J Comp Neurol. 521:3614-3665) identify four pallial and two subpallial gene expression domains and demonstrate that the mesopallium and adjoining divisions of the hyperpallium (hyperpallium intercalatum and hyperpallium densocellulare), have very similar gene expression profiles to each other, distinct from those of the nidopallium, the arcopallium, and the more distant divisions of the hyperpallium (hyperpallium apicale). The study proposes an update of the current nomenclature (Jarvis et al. [2005] Nat Rev Neurosci. 6:151-159). The authors perform densitometric quantifications of the in situ expression of 50 selected genes, use correlations of distances between vectors that represent these gene expression patterns within the 23 avian brain regions of their study, and group them according to similarity in their expression profiles. The generated cluster tree further supports their argument for a new terminology. The authors hypothesize that the mesopallium and adjoining divisions of the hyperpallium have a common developmental origin, and in the accompanying paper (Chen et al. [2013] J Comp Neurol. 521:3666-3701) show that these structures/subdivisions initially form continuous gene expression domains. With subsequent development these domains fold into distinct subdivisions in the dorsal and ventral avian pallium, forming mirror images to each other. Jarvis et al. ([2013] J Comp Neurol. 521:3614-3665) also demonstrate interesting principles of the functional organization of the avian brain by showing that specific sensory stimulation or motor behavior elicits gene expression in functional units perpendicular to the axis of the gene expression reversal and compare their arrangements and cell types with mammalian cortical columns.

Intervención educativa encaminada a prevenir la sífilis. Policlínico Gustavo Aldereguía 2009-2010 / Educational Intervention Guided to Prevent Syphilis. Dr. Gustavo Aldereguía Policlinic 2009-2010

La sífilis es una enfermedad infectocontagiosa, producida por el Treponema Pallidum, de transmisión fundamentalmente sexual, con gran afectación de la piel. Sin tratamiento se producen daños a nivel cardiovascular, óseo y neurológico, que pueden causar la muerte. Se realizó un estudio descriptivo en la población del policlínico Dr. Gustavo Aldereguía Lima del municipio Tunas, en el periodo del 2009-2010. Este tuvo el objetivo de conocer la incidencia de la sífilis para elaborar un plan de acciones educativas, encaminadas a prevenir esta situación de salud, que está incidiendo en nuestro medio. El universo lo constituyó todos los pacientes adultos que se realizaron serología, para un total de 2200 pacientes y la muestra de 200 pacientes con serología positiva. A todas las personas estudiadas se les pidió su consentimiento y fueron encuestados, teniendo en cuenta las siguientes variables: edad, sexo, escolaridad y conducta sexual. Toda la información recopilada se analizó estadísticamente por el sistema Epinfo.06, determinándosele cálculo de porcentaje. Los resultados se expusieron en tablas de contingencia de 2 x 2, lo cual permitió determinar que el grupo de 30-35 años predomino en las serologías positivas, el 68 porciento de los pacientes desconocía los aspectos relacionados con la sífilis, la mayoría de los casos no se protegían y predominó el grupo con nivel de escolaridad secundaria (AU)

Syphilis is an infectious contagious disease produced by the Treponema Pallidum, mainly of sexual transmission, with great skin affection. If it is not treated, cardiovascular, bone and neurological damages are produced and may cause death. So, a descriptive study was carried out in the population from Dr. Gustavo Aldereguía policlinic in Las Tunas municipality, from 2009 to 2010, with the objective to know the incidence of syphilis and so design a plan of educational actions directed to prevent this health situation. The universe was made up by all the adults who were tested: 2 200 patients and the sample consists of 200 patients who were positive to the serology test. All the persons studied were asked for consent and were surveyed having into consideration the following variables: age, sex, educational level and sexual behaviour. All the compiled information was analyzed statistically by Epinfo.6 system, determining the percentage calculation. The results were exposed in 2 X 2 contingency tables, what allowed determining that the prevailing positive serology test group was from 30 to 35 years old, 68 percent of the patients did not know the aspects related to syphilis, most of them did not protect themselves sexually, and the group with secondary school level prevailed (AU)

Neuronal mechanisms of learning in teleost fish / Mecanismos neuronales del aprendizaje en los peces teleósteos

Se revisaron dos aproximaciones al estudio de la neurobiología del aprendizaje en peces teleósteos: lesiones cerebrales y estimulación química. Respecto al efecto de lesiones cerebrales, la literatura reporta que las ablaciones del telencéfalo producen deficiencias en habituación, mientras que las lesiones en el cerebelo afectan el condicionamiento clásico de retracción ocular y aprendizaje espacial (efectos similares observados en mamíferos sugieren que las funciones del cerebelo pudieron haber evolucionado tempranamente en la historia de los vertebrados). Áreas del Medium Pallium (MP) parecen ser vitales en el aprendizaje emocional de los peces; más aún, las funciones del MP aparentan ser similares a las de la amígdala en mamíferos. Con respecto a procesos neuroquímicos, los antagonistas de los receptores NMDA, mostraron afectar la adquisición de condicionamiento de evitación y miedo. Por último, el óxido nítrico y el guanosín monofosfato cíclico han sido relacionados con los procesos de consolidación del aprendizaje emocional.

Two predominant approaches for studying the neurobiology of learning in fish are reviewed: brain lesions and chemical stimulation. Habituation, sensitization, Pavlovian Conditioning, spatial behavior, and emotional learning are the specific processes analyzed. Regarding the effect of brain lesions, telencephalic ablations produced impairment of habituation learning; conversely, cerebellum lesions caused deficiencies in classical conditioning of eye-retraction and spatial learning (similar effects observed in mammals suggest that the functions of the cerebellum may have evolved early in vertebrate history). Medium Pallium (MP) areas have been identified as critical for emotional learning in fish. Furthermore, neurobehavioral functions of MP seem to be similar to the functions of the amygdala in mammals. Relating to neurochemical processes, NMDA receptor antagonists affected the acquisition of avoidance and fear conditioning in a dose-dependent manner. Alternatively, Nitric Oxide (NO) and cyclic Guanosine Monophosphate (cGMP) seem to be involved in the consolidation process of emotional learning.

L-histidine reduces inhibitory avoidance in Carassius auratus submitted to cerebellar ablation

The effect of post-training treatment with L-histidine (LH) on the memory consolidation of inhibitory avoidance was investigated in Carassius auratus submitted to cerebellar ablation. The inhibitory avoidance procedure included 3 days: one habituation day, one training day (5 trials, T1-T5) and one test day. On the training day, each fish was placed individually in a white compartment separated from a black compartment by a sliding door. When the fish crossed into the black compartment, a weight was dropped in front of it (aversive stimulus) and the time to cross was recorded. Saline or LH (100 mg/kg) was injected intraperitoneally 10 min after the trials. Data were log10 transformed and analyzed by ANOVA and the Student-Newman-Keuls test (P < 0.05). In T5, all groups [ablation/LH (N = 15; 189.60 ± 32.52), ablation/saline (N = 14; 204.29 ± 28.95), sham/LH (N = 14; 232.36 ± 28.15), and sham/saline (N = 15; 249.07 ± 25.82)] had similar latencies that were significantly higher than T1 latencies [ablation/LH (89.33 ± 20.41), ablation/saline (97.00 ± 25.16), sham/LH (73.86 ± 18.42), and sham/saline (56.71 ± 17.59)], suggesting acquisition of inhibitory avoidance. For the test, there was a significant reduction in latencies of ablation/LH (61.53 ± 17.70) and sham/saline (52.79 ± 25.37) groups compared to the ablation/saline (213.64 ± 29.57) and sham/LH (199.43 ± 24.48) groups, showing that cerebellum ablation facilitated retention of inhibitory avoidance and LH reversed the effect of ablation. The results support other evidence that LH impairs memory consolidation and/or reduces the interpretation of aversion value.