Posttraumatic parkinsonism

Development of parkinsonian features following a blunt head injury in a 37-year-old man is described. High definition computed tomography scan of the midbrain demonstrated low-density lesions in the region of substantia nigra.     

Intracerebral administration of antisense oligodeoxynucleotides to GAD65 and GAD67 mRNAs modulate reproductive behavior in the female rat

Increased GABA activity in the medial hypothalamus (HYP) and midbrain central gray (MCG), but not the preoptic area (POA), facilitates sexual receptivity in the female rat [40]. In the current experiments, ovariectomized females were chronically treated with estrogen (via silastic capsules) to maintain a continuously high level of lordosis response. Administration of crystalline antisense oligodeoxynucleotide to the GABA synthetic enzyme, GAD₆₇, into the HYP and MCG significantly and reversibly reduced lordosis response for 1–2 days, but did not inhibit lordosis when administered into the POA. Administration of a control oligonucleotide, consisting of the same nucleotide bases but in a scrambled sequence, did not significantly modulate behavior when infused into any brain areas. When oligodeoxynucleotide antisense to GAD₆₇ was suspended in oil and then infused into the HYP or MCG it was more effective and resulted in less inter-animal variability. Subsequent experiments involving infusions into the MCG compared the effectiveness of antisense oligonucleotides to the two different forms of GAD, known as GAD₆₅ and GAD₆₇. Oligodeoxynucleotides antisense to the mRNA for either gene were effective at reducing lordosis behavior but with a different time course. Oligonucleotide antisense to GAD₆₇ significantly reduced behavior within 24 h of infusion and there was full recovery by 4 days post-infusion. GAD₆₅ antisense oligonucleotide did not significantly reduce behavior until 48 h post infusion and animals did not fully recover to pretest levels of lordosis until 5 days post-infusion. When antisense oligonucleotide for the two genes was administered simultaneously, the inhibition of lordosis was maximal at 24 h and stayed depressed for 4 days. There did not appear to be an additive effect of the two different antisense oligonucleotides when administered together. Tissue GABA levels in HYP and MCG of individual rats assayed by HPLC were no longer correlated with lordosis score after antisense oligonucleotide infusion but were after infusions of scrambled control oligos. Immunoblotting for the two forms of GAD revealed that GAD₆₇ antisense oligonucleotide infusion led to significant decreases in both GAD₆₇ and GAD₆₅ protein levels as compared to infusions of scrambled control oligo. In addition, the levels of a neuronal marker, neuron-specific enolase, also decreased (although nonsignificantly) suggesting either a temporary shutdown of protein synthesis or a degeneration of GABAergic neurons after GAD₆₇ antisense oligonucleotide infusion.     

The Study of Deep Brain Structures by Transcranial Duplex Sonography and Imaging Resonance Correlation

Transcranial duplex sonography (TCS) currently provides us with images of deep brain structures with sufficient resolution. We chose 2 sonographic quantitative parameters: the diameter of the third ventricle and a measurement not used by TCS to date, the midbrain area. Their reliability and reproducibility were assessed using magnetic resonance imaging (MRI) as the reference. A total of 99 patients free from neurodegenerative disorders were examined using TCS, and both parameters were measured by 2 independent explorers. Measurements of third-ventricle diameter by TCS showed very good correlation (r = 0.80) and agreement (ICC = 0.89) with measurements obtained by MRI. Measurements of the midbrain area by TCS also provided acceptable values with moderate correlation (r = 0.36) and agreement (ICC = 0.53). Interexplorer correlation values were good (ICC = 0.98 and 0.79 for the third ventricle and midbrain areas, respectively). Further studies will be required to determine the potential diagnostic usefulness of these parameters.     

猫中脑损伤后细胞凋亡及相关基因表达的意义

目的　为探索脑干损伤后影响伤情进展的分子基础。方法　建立猫中脑损伤的实验动物模型； 应用末端标记法检测损伤后的细胞凋亡； 应用原位杂交观察神经生长因子和热休克蛋白７０（ Ｈ Ｓ Ｐ７０） ｍ Ｒ Ｎ Ａ 的表达水平； 应用神经功能缺失记分观察猫神经行为学的改变。结果　不同类型的中脑损伤可以在早期诱导 Ｎ Ｇ Ｆ 和 Ｈ Ｓ Ｐ７０ ｍ Ｒ Ｎ Ａ 的表达增强， 与神经元损伤后自身保护及修复能力的产生、代偿机制的形成有关。中脑损伤后可以引起其程序性细胞死亡， 其峰值在损伤后的４８ ～７２ 小时， 这个变化时相与神经行为学上的迟发加重相一致。结论　中脑损伤后 Ｎ Ｇ Ｆ 和 Ｈ Ｓ Ｐ７０ ｍ Ｒ Ｎ Ａ 的表达水平可以反映神经元损伤的程度和自身代偿与修复的能力； 程序性细胞死亡是神经元损伤后迟发加重的重要基础。     

Rats selectively bred for high and low swim-test activity show differential responses to dopaminergic drugs

Rationale: Selective breeding of Sprague-Dawley rats has been used to generate a line of animals with very low swim-test activity (SwLo) in an attempt to model certain characteristics of depression. For comparison with the SwLo animals, a line bred for high swim-test activity (SwHi) and a non-selectively bred line (SwNS) have been generated. Previous studies using these lines suggested an inverse relationship between dopamine (DA) function in the brain and inactivity in the swim test. Objectives: The current experiments investigated the possibility that SwLo and SwHi rats show differences in central DA processes, as suggested by responsiveness to DA agonists. Results: The increase in ambulation produced by d-amphetamine (0.25– 1.0 mg/kg) was largest in SwHi rats and smallest in SwLo rats, with SwNS rats showing an intermediate response. Amphetamine levels in plasma and brain tissue were similar in SwHi and SwLo rats, indicating that pharmacokinetic differences were not responsible for the behavioral differences. Repeated amphetamine administration produced enhancement in the ambulation-increasing effects of this drug (i.e., sensitization), with significant enhancement seen in all three lines. Apomorphine in doses that stimulate postsynaptic receptors (0.25– 4.0 mg/kg) produced mainly increased sniffing behaviors in SwHi and SwNS rats and oral behaviors in SwLo rats, suggesting that the lines differ in proportions of D1, D2, and D3 postsynaptic receptors. Conclusions: The findings suggest that DA function differs in lines of rats selectively bred for differences in swim behavior, a feature that may make these lines useful for studying certain depressive symptoms that might be related to DA function. Received: 26 September 1998 / Final version: 28 May 1999     

The neurobiology of sound-specific auditory plasticity: A core neural circuit

Auditory learning or experience induces large-scale neural plasticity in not only the auditory cortex but also in the auditory thalamus and midbrain. Such plasticity is guided by acquired sound (sound-specific auditory plasticity). The mechanisms involved in this process have been studied from various approaches and support the presence of a core neural circuit consisting of a subcortico-cortico-subcortical tonotopic loop supplemented by neuromodulatory (e.g., cholinergic) inputs. This circuit has three key functions essential for establishing large-scale and sound-specific plasticity in the auditory cortex, auditory thalamus and auditory midbrain. They include the presence of sound information for guiding the plasticity, the communication between the cortex, thalamus and midbrain for coordinating the plastic changes and the adjustment of the circuit status for augmenting the plasticity. This review begins with an overview of sound-specific auditory plasticity in the central auditory system. It then introduces the core neural circuit which plays an essential role in inducing sound-specific auditory plasticity. Finally, the core neural circuit and its relationship to auditory learning and experience are discussed.     

Serotonergic hyperinnervation and effective serotonin blockade in an FGF receptor developmental model of psychosis

The role of fibroblast growth factor receptors (FGFR) in normal brain development has been well-documented in transgenic and knock-out mouse models. Changes in FGF and its receptors have also been observed in schizophrenia and related developmental disorders. The current study examines a transgenic th(tk-)/th(tk-) mouse model with FGF receptor signaling disruption targeted to dopamine (DA) neurons, resulting in neurodevelopmental, anatomical, and biochemical alterations similar to those observed in human schizophrenia. We show in th(tk-)/th(tk-) mice that hypoplastic development of DA systems induces serotonergic hyperinnervation of midbrain DA nuclei, demonstrating the co-developmental relationship between DA and 5-HT systems. Behaviorally, th(tk-)/th(tk-) mice displayed impaired sensory gaiting and reduced social interactions correctable by atypical antipsychotics (AAPD) and a specific 5-HT2A antagonist, M100907. The adult onset of neurochemical and behavioral deficits was consistent with the postpubertal time course of psychotic symptoms in schizophrenia and related disorders. The spectrum of abnormalities observed in th(tk-)/th(tk-) mice and the ability of AAPD to correct the behavioral deficits consistent with human psychosis suggests that midbrain 5-HT2A-controlling systems are important loci of therapeutic action. These results may provide further insight into the complex multi-neurotransmitter etiology of neurodevelopmental diseases such autism, bipolar disorder, Asperger's Syndrome and schizophrenia.     

Regional gray matter abnormalities in panic disorder: A voxel-based morphometry study

Although abnormalities in brain structures involved in the neurobiology of fear and anxiety have been implicated in the pathophysiology of panic disorder (PD), relatively few studies have made use of voxel-based morphometry (VBM) magnetic resonance imaging (MRI) to determine structural brain abnormalities in PD. We have assessed gray matter volume in 19 PD patients and 20 healthy volunteers using VBM. Images were acquired using a 1.5 T MRI scanner, and were spatially normalized and segmented using optimized VBM. Statistical comparisons were performed using the general linear model. A relative increase in gray matter volume was found in the left insula of PD patients compared with controls. Additional structures showing differential increases were the left superior temporal gyrus, the midbrain, and the pons. A relative gray matter deficit was found in the right anterior cingulate cortex. The insula and anterior cingulate abnormalities may be relevant to the pathophysiology of PD, since these structures participate in the evaluation process that ascribes negative emotional meaning to potentially distressing cognitive and interoceptive sensory information. The abnormal brain stem structures may be involved in the generation of panic attacks.