WT and BDNF+/− mice do not differ in the pattern of running.

<p>The pattern of average running activity for mice over the duration of the 90-day experimental period. Points represent the average total running activity for WT or BDNF+/− mice for each 24 hour period ± SEM.</p

Exercise does not protect against MPTP-induced SN DA neurotoxicity in BDNF +/− mice.

<p>(A) Representative photomicrograph of the SNpc of C57BL/6 mouse at the level of the medial longitundinal fasciculus (mlf). (B) Representative photomicrograph of the SNpc of BDNF+/− mouse at the level of the medial longitundinal fasciculus (mlf). (C) Representative photomicrograph of the SNpc of the C57BL/6 mouse 7 days following MPTP mouse at the level of the mlf. (D) Representative photomicrograph of the SNpc of the BDNF+/− mouse allowed 3 months exercise and then treated with MPTP. There is no difference in the appearance of the sedentary MPTP-treated C57BL/6 mouse and the BDNF+/− mouse allowed exercise. (E) BDNF+/− mice allowed free access to running wheels for 90 days prior to MPTP administration lost significantly greater SN DA neurons than exercising WT littermates. Bars represent the average ± SEM; <b>*</b> p<0.01 as compared to WT SH+Sal; + p<0.01 as compared to WT Ex+MPTP.</p

List of Microsatellite Markers and Mendelian Correlations.

<p>List of Microsatellite Markers and Mendelian Correlations.</p

Neurochemical Measurement of Adenosine in Discrete Brain Regions of Five Strains of Inbred Mice

<div><p>Adenosine (ADO), a non-classical neurotransmitter and neuromodulator, and its metabolites adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP), have been shown to play an important role in a number of biochemical processes. Although their signaling is well described, it has been difficult to directly, accurately and simultaneously quantitate these purines in tissue or fluids. Here, we describe a novel method for measuring adenosine (ADO) and its metabolites using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Using this chromatographic technique, we examined baseline levels of ADO and ATP, ADP and AMP in 6 different brain regions of the C57BL/6J mouse: stratum, cortex, hippocampus, olfactory bulb, substantia nigra and cerebellum and compared ADO levels in 5 different strains of mice (C57BL/6J, Swiss-Webster, FVB/NJ, 129P/J, and BALB/c). These studies demonstrate that baseline levels of purines vary significantly among the brain regions as well as between different mouse strains. These dissimilarities in purine concentrations may explain the variable phenotypes among background strains described in neurological disease models.</p></div

Chromosomal maps showing the identified QTL regions.

<p>A 20 cM region (red box) on the distal are of mCHr 5 and the proximal arm of mChr14 were identified by QTL analysis.</p

Identification of optimal parameters for simultaneous detection of ADO, ATP, ADP and AMP.

<p>(A) To determine the optimum voltage necessary to fully oxidize ADO, ATP, ADP and AMP, we measured the number of oxidized molecules at voltages ranging from +700–+1700 mV. Construction of a hydrodynamic voltamogram (HDV), necessary to determine the optimal signal/noise (s/n) ratio, showed that +1300 mV was optimum for the simultaneous detection of the compounds. (B) To determine the accurate range and linearity of detection of ADO, ATP, ADP, and AMP, 0–100 ng of each standard was injected into the HPLC. Electrochemical detection of the oxidized molecules shows a linear slope for each of the compounds. (C) Representative chromatograms of simultaneous separation of ADO, ATP, ADP and AMP demonstrating linearity of the injected analytes.</p

Protein changes identified by 2D gel electrophoresis following 3 months of exercise in the substantia nigra and striatum of BDNF +/− and Wt mice.

<p>Protein changes identified by 2D gel electrophoresis following 3 months of exercise in the substantia nigra and striatum of BDNF +/− and Wt mice.</p

Representative gel of PCR products for genotyping.

<p>WT animals were identified by the presence of one band at ∼275 base pairs, while BDNF+/− mice were identified by the presence of both the ∼275 base pair band and a unique band at ∼340 base pairs.</p

Quantitation of ADO in 7 regions of the brain in 5 strains of mice.

<p>ANOVA demonstrated significant differences between mouse strains in each region examined. Post-hoc Bonferroni comparisons are shown for each brain region. N = 10 for each measurement.</p

WT and BDNF+/− mice do not differ in the amount of running.

<p>Average total running activity for WT and BDNF+/− mice during the (A) daytime, (B) nighttime or (C) the total 24 hour interval. (D) The average total running distance for WT and BDNF+/− mice at 30 day intervals. Bars indicate the average of total running activity ± SEM.</p