European Journal of Neuroscience最新文献

Gut inflammation is a salient prodromal feature of Parkinson's disease (PD) implicated in pathologic processes leading to nigrostriatal dopaminergic degeneration. However, existing rodent models of PD are suboptimal for investigating the interaction between gut inflammation and neuropathology. This study aimed to develop a rat model of PD in which gut inflammation exacerbated PD symptoms induced by a parkinsonian lesion. This was achieved by combining the 6-hydroxydopamine (6-OHDA) rat model for PD and the dextran sodium sulfate (DSS) rat model for colitis. The model was characterised using behavioural tests, including reaching, step, gait, open-field and cylinder tests, plus stereological quantification of substantia nigra (SN) DA neurodegeneration, and histological analysis of SN microglial activation and distal colon morphology. The combination of 6-OHDA and DSS resulted in greater stool softening and bleeding, shorter colons and greater distal colon histological damage, when compared with the 6-OHDA model. Additionally, 6-OHDA and DSS rats displayed similar DA neurodegeneration, yet less SN microglial activation, when compared to 6-OHDA rats that did not receive DSS. Finally, DSS + 6-OHDA rats exhibited impaired forelimb motor function compared with 6-OHDA rats, with decreased performance in reaching and step tests. In conclusion, DSS administration exacerbated forelimb motor dysfunction in 6-OHDA rats. Behavioural changes in DSS + 6-OHDA rats were associated with lower levels of microglial activation and similar levels of dopamine depletion compared with 6-OHDA-only rats. These results support that the DSS + 6-OHDA rat model is a promising PD animal model to investigate deleterious gut–brain interactions in PD.

Traumatic brain injury is one of the most common cerebral incidences worldwide. Repetitive mild traumatic brain injuries occurring, for example, in athletes or victims of abuse, can cause chronic neurodegeneration due to neuroinflammation, in which the crosstalk between reactive astrocytes and activated microglia is crucial for modulating neuronal damage. The inducible enzyme heme oxygenase-1 and its product carbon monoxide are known to be ascribed neuroprotective and anti-inflammatory properties. We caused repetitive mild traumatic brain injuries in wild-type mice compared to mice without microglial heme oxygenase-1 expression. Additionally, mice were treated daily with either air or carbon monoxide exogenously. In wild-type mice, we observed enhanced microglia activation and astrogliosis as well as vasodilation after repetitive trauma. In heme oxygenase-1 knockout mice, we observed enhanced activation of microglia and astrocytes at baseline pretrauma with a lack of an adequate inflammatory response to repetitive injury. However, the knockout led to enhanced NF-κB and IFNγ expression in the post-trauma period. Carbon monoxide exerted neuroprotection, as suggested by reduced wake-up times in mice and by beneficially altering inflammation post-traumatic brain injury. This study further underlines the crucial role of the heme oxygenase-1/carbon monoxide system in the modulation of neuronal damage and the associated neuroinflammatory response after repetitive traumatic brain injury.

Timing and architecture of sleep are co-driven by circadian rhythms modulated by their major Zeitgeber light and darkness. In a natural environment, one is exposed to 3.000 lx (cloudy winter sky) to 100.000 lx (bright sunny sky). The aim of the study was to assess (1) habitual daytime light exposure in urban winter and (2) impact of daytime urban light on objective night-time sleep. Eleven healthy participants (mean age ± SD: 25.4 ± 2.8 years; 6 male) wore eyeglass frames continuously recording daytime illuminance levels vertically to the eye by mounted sensors (range: 1–40.000 lx) during four consecutive days in winter 2008 in Berlin, Germany. In-lab polysomnography was performed over two nights in nine participants. Median light exposure over 4 days was the following: full day 7:00–19:00 h: 23 lx (12–37 lx); morning 7:00–11:00 h: 81 lx (19–201 lx); midday 11:00–15:00 h: 68 lx (19–164 lx); afternoon 15:00–19:00 h: 22 lx (6–58 lx), resulting in only 36 min > 500 lx per day. Timing of daytime light intensity was significantly associated with subsequent sleep: lower midday illuminance with shorter REM latency (Rho = 0.817; p = 0.049) and earlier REM polarity (less prevalence of REM at end-of-sleep; Rho = 0.817; p = 0.049). Humans, living in an urban environment, appear to be exposed to extremely low light levels, which we named as ‘Living in Biological Darkness’. Most fascinating, physiology seems to adapt and responds to variation in light intensity on such low levels. Interestingly, the observed changes in sleep architecture with low light levels are reminiscent of those suspected to constitute biological markers of depression some 40–50 years ago.

Communication sound processing in mouse AC is lateralized. Both left and right AC are highly specialised and differ in auditory stimulus representation, functional connectivity and field topography. Previous studies have highlighted intracortical functional circuits that explain hemispheric stimulus preference. However, the underlying microstructure remains poorly understood. In this study, we examine structural lateralization of AC on the basis of immunohistochemically stained and tissue-cleared adult mouse brains (n = 11). We found hemispheric asymmetries of intracortical myelination, most prominently in layer 2/3, which featured more intercolumnar connections in the right AC. Furthermore, we found a larger structural asymmetry in the right AC. We also investigated sex differences. In male mice, myelination direction in the right AC is tilted to the anterior side. This pattern is inverted in female mice. However, the spatial distribution of neuronal cell bodies in the left and right AC along the laminar axis of the cortex was remarkably symmetric in all samples. These results suggest that basic developmentally defined structures such as cortical columns remain untouched by lateral specialisation, but more plastic myelinated axons show diverse hemispheric asymmetries. These asymmetries may contribute to specialisation on lateralized tasks such as vocal communication processing or specialisation on spectral or temporal complexity of stimuli.

Lightly touching a solid object reduces postural sway. Here, we determine the effect of artificially modifying haptic feedback for balance. Participants stood with their eyes closed, lightly gripping a manipulandum that moved synchronously with body sway to systematically enhance or attenuate feedback gain between +2 and −2, corresponding to motion in the same or opposite direction to the body, respectively. This intervention had a systematic effect on postural sway, which exhibited an asymmetric u-shape function with respect to haptic feedback gain. Sway was minimal around zero gain, corresponding to a static object. Sway increased slightly at gains below −0.25 but increased greatly at gains above +0.25. At +2, it was approximately double that of a no-touch condition. Mean interaction force between the hand and manipulandum remained < 0.9 N throughout, although it increased slightly at extreme gains. Cross-correlations between hand force and trunk position were highest during conditions of least sway, suggesting that higher quality haptic feedback is associated with greater sway reduction. We successfully replicated the sway behaviour using a feedback control model that attenuated haptic feedback signals when the discrepancy between haptic and proprioceptive signals reached a threshold. Our findings suggests the CNS can utilise augmented haptic feedback for balance, but only with relatively small changes to natural feedback gain. In healthy volunteers, it offers minimal benefit over a static object. Haptic feedback is therefore optimal when motion is physiologically realistic and subtle enough to be misinterpreted as self-motion.