Tangential Intrahypothalamic Migration of the Mouse Ventral Premamillary Nucleus and Fgf8 Signaling

The tuberal hypothalamic ventral premamillary nucleus (VPM) described in mammals links olfactory and metabolic cues with mating behavior and is involved in the onset of puberty. We offer here descriptive and experimental evidence on a migratory phase in the development of this structure in mice at E12.5–E13.5. Its cells originate at the retromamillary area (RM) and then migrate tangentially rostralward, eschewing the mamillary body, and crossing the molecularly distinct perimamillary band, until they reach a definitive relatively superficial ventral tuberal location. Corroborating recent transcriptomic studies reporting a variety of adult glutamatergic cell types in the VPM, and different projections in the adult, we found that part of this population heterogeneity emerges already early in development, during tangential migration, in the form of differential gene expression properties of at least 2–3 mixed populations possibly derived from subtly different parts of the RM. These partly distribute differentially in the core and shell parts of the final VPM. Since there is a neighboring acroterminal source of Fgf8, and Fgfr2 is expressed at the early RM, we evaluated a possible influence of Fgf8 signal on VPM development using hypomorphic Fgf8neo/null embryos. These results suggested a trophic role of Fgf8 on RM and all cells migrating tangentially out of this area (VPM and the subthalamic nucleus), leading in hypomorphs to reduced cellularity after E15.5 without alteration of the migrations proper.

The Impact of Cerebral Amyloid Angiopathy in Various Neurodegenerative Dementia Syndromes: A Neuropathological Study

Purpose. The Boston criteria for cerebral amyloid angiopathy (CAA) have to be confirmed by postmortem examination. The present study investigates the incidence and the cerebrovascular impact of the severity of CAA in various neurodegenerative dementia diseases.Material and Methods. 208 patients underwent an autopsy. They consisted of 92 brains with Alzheimer’s disease (AD), 46 with frontotemporal lobar degeneration (FTLD), 24 with progressive supranuclear palsy (PSP), 21 with Lewy body dementia (LBD), 5 with corticobasal degeneration (CBD), and 20 controls. In addition to the macroscopic examination, a whole coronal section of a cerebral hemisphere, at the level of the mamillary body, was taken for semiquantitative microscopic evaluation of the small cerebrovascular lesions.Results. CAA is present in 2/3% of the AD brains of which half of them have a severe form, grade 3. Only the latter displays more cerebrovascular lesions. CAA is present in 45% of the LBD brains. Cortical microinfarcts are only more frequent in the CAA grade 3 group. In LBD additional AD pathology is present in 41% of the CAA grade 0, 83% in grade 1-2, and 100% in grade 3. In PSP only 21% had CAA grade 1-2. In FTLD, CBD, and normal controls no CAA pathology is observed.Conclusions. The present study shows that CAA is most frequently associated to AD but that only the severe form displays more cerebrovascular lesions. LBD is the second most frequent disease associated to CAA with a clear correlation between the incidence of the associated AD features and the increasing severity of the CAA. In PSP only 21% display mild CAA features. PSP, tau-FTLD, and CBD are part of the Pick complex diseases, who are known to have a favourable vascular profile which can explain their low incidence of cerebrovascular lesions, in contrast to AD and LBD brains.

104 Distribution of Gonadotropin-Releasing Hormone and Kisspeptin Neurons in the Preoptic Area and Hypothalamus During the Estrous Cycle in Cows

Gonadal steroids hormones indirectly regulate gonadotropin-rleasing hormone (GnRH) secretion. Kisspeptin (Kp) co-expresses steroid receptors and modulates GnRH release. The objective of the study was to characterise the number and proportion of GnRH and Kp immunoreactive cells and their association in the preoptic area (POA) and hypothalamus during different phases of the oestrous cycle in cows. Daily ovarian ultrasonography was performed to detect follicle development and ovulation (Day 0) after prostaglandin treatment. On Day 5, cows were assigned randomly to the following groups: proestrus (n = 2), metestrus (n = 2) or diestrus (n = 3). Cows in the diestrus group were killed on Day 8. Cows in the proestrus and metestrus groups were given luteolytic dose of prostaglandin on Day 5.5 and Day 6 and were killed on Day 7 and 24 h after the ensuing ovulation, respectively. Cow heads were perfused with 4% paraformaldehyde via the carotid arteries to fix the brain in situ. The brain-stem (rostral portion of the POA to the mamillary body) was isolated by dissection and placed in 4% paraformaldehyde for 48 h. Following cryoprotection, the tissue block containing the POA and hypothalamus was frozen at –80°C and sectioned serially at a thickness of 50 mm using a cryostat microtome. Every 20th free-floating section was processed for double labelling using 2 sequential immuno-peroxidase reactions and ABC staining; Kp was immuno-labelled with Nickel-DAB at a dilution of 1:10,000 rabbit anti-kisspeptin (AC566, INRA, France), and GnRH was stained with DAB using 1:40,000 rabbit anti-GnRH (LR-5, Dr Benoit). The numbers of neuron cell bodies and fibres were recorded in different areas of the POA and the hypothalamus by brightfield microscopy using 10× and 40× objective lenses. Data were compared among groups by ANOVA. Major aggregations of Kp cells were localised in the mPOA, OVLT, and ARC. Overall, the number of Kp cells was higher in the metestrus v. diestrus group (719 ± 94 v. 378 ± 8; P = 0.01), but was similar to the proestrus group (558 ± 9). The number of Kp cells in the POA (mPOA, OVLT) tended to be higher in the metestrus v. diestrus group (395 ± 56 v. 147 ± 44; P = 0.06), and was intermediate in the proestrus group (206 ± 6). The number of Kp cells in the ARC did not differ among groups (metestrus 310 ± 26, diestrus 206 ± 53, proestrus 321 ± 99; P = 0.4). The number of GnRH cells bodies was not different among groups (metestrus 40 ± 3, diestrus 50 ± 9, proestrus 43 ± 8; combined; P = 0.8), and the distribution was higher in the POA (metestrus 25 ± 2, diestrus 30 ± 3, proestrus 33 ± 2) than hypothalamus. The proportion of GnRH cells in apposition to Kp fibres tended to be highest in the proestrus v. metestrus and diestrus groups (50.5 ± 1% v. 34.1 ± 9% and 31.4 ± 3%; P = 0.09). In conclusion, the number of Kp immunoreactive cells, but not GnRH cells, present in the POA and hypothalamus changed among different phases of the oestrous cycle due primarily to an increase in number of Kp cells in POA during metestrus. The proestrous phase was associated with an increase in apposition between Kp fibres and GnRH cells.