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Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood–brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 downregulation was sufficient to induce depression-like behaviors following subthreshold social stress whereas chronic antidepressant treatment rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or mice injected with adeno-associated virus expressing shRNA against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across the BBB and depression. Chronic social defeat stress induces loss of protein claudin-5, leading to abnormalities in blood vessel morphology, increased blood brain barrier permeability, infiltration of immune signals and depression-like behaviors.

Heightened aggression is characteristic of multiple neuropsychiatric disorders and can have various negative effects on patients, their families and the public. Recent studies in humans and animals have implicated brain reward circuits in aggression and suggest that, in subsets of aggressive individuals, domination of subordinate social targets is reinforcing. In this study, we showed that, in male mice, orexin neurons in the lateral hypothalamus activated a small population of glutamic acid decarboxylase 2 (GAD2)-expressing neurons in the lateral habenula (LHb) via orexin receptor 2 (OxR2) and that activation of these GAD2 neurons promoted male–male aggression and conditioned place preference for aggression-paired contexts. Moreover, LHb GAD2 neurons were inhibitory within the LHb and dampened the activity of the LHb as a whole. These results suggest that the orexin system is important for the regulation of inter-male aggressive behavior and provide the first functional evidence of a local inhibitory circuit within the LHb.Flanigan et al. show that activation of inhibitory neurons in the lateral habenula by the neuropeptide orexin (hypocretin) promotes both inter-male aggression and conditioned place preference for contexts associated with winning aggressive contests.

The LOU/C/Jall (LOU) rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW) throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6-42 months) were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning, and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL) male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR) prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR) rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn), an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non-obese aging rats.

Heightened aggression is characteristic of multiple neuropsychiatric disorders and can have a wide variety of negative effects on patients, their families, and the public. Recent studies in humans and animals have implicated brain reward circuits in aggression and suggest that, in subsets of aggressive individuals, repeated domination of subordinate social targets is reinforcing. Here, we show that orexin neurons originating from the lateral hypothalamus activate a small population of GABAergic interneurons in the lateral habenula (LHb) via orexin receptor 2 (OxR2) to promote aggression and conditioned place preference (CPP) for aggression-paired contexts. Our study suggests that the orexin system is a potential target for the development of novel therapies aimed at reducing aggressive behaviors and provides the first functional evidence of a local inhibitory circuit within the LHb.

Things were not boding well for a phone call from the Orioles brass. But down in Triple-A with the International League's Ottawa Lynx, [Adam Loewen] rediscovered his control. In three games with the lame duck Lynx, covering 21 innings, Loewen walked only three hitters, also giving up only 11 hits, while keeping his earned-run average under two. Orioles fans can only hold out hope for the future, for their Birds are bound for their ninth consecutive fourth-place finish in the AL East. Pitching-wise, [Erik Bedard], [Daniel Cabrera] and Loewen -- who took journeyman Bruce Chen's place in the starting rotation -- represent the franchise's future. \"The Prince of Whalley\" is in Baltimore to stay. That attitude can be traced back to the diamonds of Surrey, and specifically Whalley, where Loewen's talent developed in one of the best minor baseball associations in Canada. Whalley Little League celebrated its 50th anniversary this year in fine style, hosting the Canadian championships and seeing its own team repeat as champions. Whalley's little leaguers went 1-2 last week in Williamsport, Pa., wrapping up play with a 2-1 win over Saipan.

Things were not boding well for a phone call from the Orioles brass. But down in Triple-A with the International League's Ottawa Lynx, [Adam Loewen] rediscovered his control. In 21 innings over three games with the lame-duck Lynx, Loewen walked only three hitters and gave up 11 hits, while keeping his earned-run average under two. Orioles fans can only hold out hope for the future, for their Birds are bound for their ninth consecutive fourth-place finish in the AL East. Pitching-wise, [Erik Bedard], [Daniel Cabrera] and Loewen -- who took journeyman Bruce Chen's place in the starting rotation -- represent the franchise's future. \"The Prince of Whalley\" is in Baltimore to stay. That attitude can be traced back to the diamonds of Surrey, and specifically Whalley, where Loewen's talent developed in one of the best minor baseball associations in Canada. Whalley Little League celebrated its 50th anniversary this year in fine style, hosting the Canadian championships and seeing its own team repeat as champions. Whalley's little leaguers went 1-2 last week in Williamsport, Pa., wrapping up play with a 2-1 win over Saipan.

The story of the first period was the lack of opportunism on both sides. Loyola goalie Matthew Humes, rock-solid between the pipes yesterday, made the P.O.P. (play of the period) when he robbed the Sabres' slickest skater, Martin Proulx. Patrick Langlois opened the score for the Sabres. After Humes again robbed Proulx on a two-on-one breakaway and stoned Mathieu Daraiche with a superb glove save, the Braves' offence got busy. In midget basketball, the Loyola Warriors reclaimed the title they had lost last year in a 59-46 victory over the Lower Canada College Lions. In 21 years, it is only Loyola's second title in the category.

[Glenn Michibata] was in Montreal to prepare for this week's U.S. Professional Indoor Tournament at The Spectrum in Philadelphia, where he'll join doubles partner Grant Connell of Vancouver. \"We did well in Philly last year,\" Michibata said. \"We feel like we can win any tournament we enter. Our confidence level is that high.\" Michibata and Connell are ranked 12th in the world by the Association of Tennis Professionals.

After finishing fourth in the 200-metre breaststroke at the 1991 world championships in Perth, Australia, in January, [Cloutier] has a lofty goal for Calgary. She aims to slice a huge one second off her best times of 2:28:70 for the 200-metre event and 1:09:55 in the 100 metres. The universities of McGill, Laval, Sherbrooke, and Montreal will battle for the Hoechst Cup, emblematic of university swimming supremacy. Among participants will be McGill's Terry Dimuck, along with Montreal's Patricia Noall, Manon Simard, and Bernard Lapierre.

In juvenile, LCC's Simon Toole lost a rare race to schoolmate Peter Stotland, who clocked 21:36, almost 1 1/2 minutes ahead of Toole. However, Toole won the over-all honors with a time of 42:07, 53 seconds better than Stotland. \"Powdery snow with -5 (C) temperature is much better than all that ice and slush we skied through. It was so hard to get a grip ... but for me this is still fun,\" said bantam boys' winner Peter Wulfraat, an eighth-grader from Beaconsfield High School.